|Year : 2016 | Volume
| Issue : 1 | Page : 5-9
Effect of intensive statin therapy on coronary intervention outcomes, cardiac markers, vaspin, and adiponectin levels in elderly patients with coronary heart disease
Yan Liang1, Jun Guo2, Zhe Zhang3, Yang Li4, Yuan Zhang2
1 Department of Blood Transfusion, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
2 Department of Cardiology, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
3 Department of Cardiology, General Hospital of Guangzhou Military Command of PLA, Guangzhou, Guangdong, China
4 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China
|Date of Submission||17-Feb-2016|
|Date of Acceptance||19-Mar-2016|
|Date of Web Publication||1-Apr-2016|
Department of Blood Transfusion, The First Affiliated Hospital of Jinan University, No. 613, Huangpu Road (West), Guangzhou 510630, Guangdong
Source of Support: None, Conflict of Interest: None
Aim: To explore the effect of intensive statin therapy (different doses) on percutaneous coronary intervention (PCI) outcomes in elderly patients with coronary heart disease (CHD). Methods: In this Institutional Ethics Committee-approved study, 105 elderly patients (> 80-year-old) with CHD admitted into the First Affiliated Hospital of Jinan University from June 2012 to June 2014 were randomly divided into three groups and received 20 mg/day, 40 mg/day, or 60 mg/day atorvastatin, respectively, before PCI surgery. Postsurgical (1 month after surgery) changes in major adverse cardiovascular events (MACEs), cardiac markers, vaspin, and adiponectin levels were compared among the groups. Results: Among the study groups, the incidence of MACE and PCI-related myocardial infarction rate was the lowest in 60 mg group (2.9%) reaching significance (P < 0.05). Although postsurgical cardiac marker levels increased significantly (P < 0.05), the values were found inversely correlated to statin dose (P < 0.05). Postsurgical vaspin, adiponectin, and alanine aminotransferase levels significantly increased in 60 mg group (P < 0.05). There was no considerable difference between presurgical and postsurgical serum creatinine and blood urea nitrogen levels in any group (P > 0.05). No study subjects showed statin-related myopathy. Conclusion: The application of 60 mg/d intensive statin therapy in short term could improve outcomes of PCI in patients with elderly CHD, maintain stable levels of cardiac markers, Vaspin and adiponectin, with exact effect and good safety.
Keywords: Adipokine and adiponectin, cardiac markers, coronary heart disease, intensive statin therapy, percutaneous coronary intervention
|How to cite this article:|
Liang Y, Guo J, Zhang Z, Li Y, Zhang Y. Effect of intensive statin therapy on coronary intervention outcomes, cardiac markers, vaspin, and adiponectin levels in elderly patients with coronary heart disease. Transl Surg 2016;1:5-9
|How to cite this URL:|
Liang Y, Guo J, Zhang Z, Li Y, Zhang Y. Effect of intensive statin therapy on coronary intervention outcomes, cardiac markers, vaspin, and adiponectin levels in elderly patients with coronary heart disease. Transl Surg [serial online] 2016 [cited 2019 May 21];1:5-9. Available from: http://www.translsurg.com/text.asp?2016/1/1/5/179566
| Introduction|| |
Coronary heart disease (CHD) is a disease caused by atherosclerotic vascular stenosis and occlusion, leading to myocardial ischemia, hypoxia, and necrosis.,,, Percutaneous coronary intervention (PCI) is one of the conventional treatments for CHD, which is shown to improve the quality of life of critically ill patients. Recent studies have identified that the cardiac markers are elevated in CHD patients after PCI, which significantly increased the chances of major adverse cardiovascular events (MACEs).,, Statin drugs may play a significant role in post-PCI prognosis, but the dose selection in elderly patients is still controversial. In this study, 105 elderly patients with CHD treated with PCI were administered with different doses of atorvastatin. MACE, cardiac markers, vaspin, and adiponectin changes after surgery were assessed and analyzed.
| Methods|| |
Inclusion and exclusion criteria
The study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Jinan University. Elderly patients with CHD, admitted into the First Affiliated Hospital of Jinan University from June 2012 to June 2014, were considered for the study. Inclusion criteria were: (1) diagnosed with CHD based on the American Heart Association diagnostic criteria, (2) ≥ 80 year old, (3) elective PCI surgery success (postoperative residual stenosis lesions < 30%). Exclusion criteria were: (1) associated organ damage, (2) history of trauma or surgery in the past 3 weeks, (3) taking lipid-lowering, anti-oxidation, or statin drugs in the past 3 weeks before enrolling, (4) uncontrolled hypertension, diabetes, rheumatic disease, thyroid disease, and any other underlying diseases, (5) contraindications of statins, (6) recommended for emergency PCI treatment.
The study was a double-blinded randomized trial where both the investigators and patients were blinded of their treatment group. The patients who met all the inclusion and exclusion criteria were divided into 20 mg group, 40 mg group, and 60 mg group according to the random number table.
Study subjects were administered with long-term angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, β-receptor blockers, and other drugs after their enrollment. Aspirin and other anti-platelet aggregation drugs were withdrawn 5–10 days before PCI. Patients were orally administered with 20 mg, 40 mg, or 60 mg of atorvastatin calcium tablets (Pfizer Pharmaceutical Co., 10 mg/piece, 7/box) in accordance with their group before surgery. Routine low molecular weight heparin was administered for 3 days after surgery. Subjects continued to receive their respective doses of atorvastatin calcium tablets for 1 month after surgery.
MACE, cardiac markers, vaspin, adiponectin, liver and kidney function tests, and adverse reactions of patients in each group were assessed before PCI and 1 month after surgery.
MACE includes cardiac death and myocardial infarction (acute myocardial infarction, PCI-related myocardial infarction, and target vessel revascularization). The diagnostic criteria for PCI-related myocardial infarction, followed in this study, are briefed elsewhere. Target vessel revascularization is the condition where patient needs secondary PCI or coronary artery bypass surgery. MACE rate was compared among the groups at 1 month after surgery.
Totally, 5 mL fasting cubital vein blood was taken from each patient. Iso-enzyme of creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), and high-sensitivity C-reactive protein (hs-CRP) were detected by enzyme-linked immunosorbent assay (ELISA). Kits were purchased from Boster Biological Engineering Co., Ltd., Wuhan. Changes in cardiac markers before PCI before the patients received atorvastatin and 1 month after surgery were assessed. Normal range of CK-MB is 0–25 U/L, cTnI 0–0.5 ng/mL, and hs-CRP 0–3 mg/L.
Vaspin and adiponectin: Vaspin levels and adiponectin concentration in each group were measured using ELISA, before PCI and 1 month after surgery.
Liver and kidney function tests and adverse reactions: Olympus AU 640 large-scale automatic biochemical analyzer detector (Japan) was used to detect alanine aminotransferase (ALT), serum creatinine (SCr), and blood urea nitrogen (BUN) before PCI and 1 month after surgery in each group. The changes in liver and kidney function were analyzed. ALT normal range is 0–40 U/L, SCr normal range is 44–133 μmol/L (male) and 44–106 μmol/L (female). The occurrence of statin-related myopathy was observed during treatment of patients in each group.
All the data in this clinical study were analyzed using SPSS 18.0 statistical software (SPSS Inc., Chicago, IL, USA). Number of cases/percentage (n/%) were calculated and analyzed for statistical significance using Chi-square test. Mean ± standard deviation was recorded and analyzed for statistical significance using t-test. The α =0.05 and P < 0.05 were considered statistically significant.
| Results|| |
Study subjects and grouping
A total of 105 patients who met all the study-related criteria and willingly signed the informed consent were included in the study as study subjects providing 35 subjects for each group. Clinical data of subjects in each group are shown in [Table 1]. Age, course of disease, the time-to-PCI from enrollment, gender ratio, body mass index, and other general clinical data showed no significant difference (P > 0.05).
Major adverse cardiovascular events
One subject in 20 mg statin group passed away at 3 days after PCI because of cardiogenic shock due to thrombosis in stent. The overall incidence of MACE in 60 mg statin group was 2.9% at 1 month after PCI which was significantly < 40 mg (11.4%) and 20 mg (25.8%) in statin group (P < 0.05). PCI-related myocardial infarction rate in 60 mg group was also found to be the lowest, reaching 2.9%, compared to 40 mg and 20 mg group who were 11.4% and 20.0%, respectively [Table 2].
|Table 2: Genesis of major adverse cardiovascular events in each Group 1 month after percutaneous coronary intervention (n=35)|
Click here to view
Compared to presurgical levels, postsurgical CK-MB, cTnI, and hs-CRP levels significantly increased in all groups (P < 0.05), the values of which were found inversely proportional to the dose of statin administered that reached statistical significance (P < 0.05) [Table 3].
|Table 3: Changes in cardiac markers before percutaneous coronary intervention and 1 month after surgery (n=35, x̄; ± s)|
Click here to view
Vaspin and adiponectin
There was no considerable difference in postsurgical vaspin level between 20 mg and 40 mg statin groups (P > 0.05), while the same was significantly increased in 60 mg group (P < 0.05). Postsurgical adiponectin concentration significantly increased compared to their presurgical levels in all the groups, among which the 60 mg group reached the highest that managed to reach significance (P < 0.05) [Table 4].
|Table 4: Changes in vaspin and adiponectin before percutaneous coronary intervention and 1 month after surgery (n=35, x̄ ± s)|
Click here to view
Liver and kidney function analysis and adverse reactions
Postsurgical ALT levels significantly increased in all the groups, with 60 mg group reaching the highest (P < 0.05). In none of the groups, the ALT level reached > 3 times the normal value. ALT level was effectively controlled after administering liver-protecting drugs. There was no significant difference in SCr and BUN levels, both before and 1 month after surgery (P > 0.05) [Table 5]. None of the patients showed statin-related myopathy.
|Table 5: Changes in liver and kidney function before percutaneous coronary intervention and 1 month after surgery (n=35, x̄ ± s)|
Click here to view
| Discussion|| |
The incidence of CHD shows rapidly increasing trend, causing a direct result in declining level of the national labor force, reducing quality of life, and rising burden of disease. With the PCI procedure extensively applied clinically, the prognosis in patients with CHD has been improved to some extent. However, cardiac markers are known to rise after PCI in some patients which increase the incidence of MACE. Preiss et al. pointed out that this was related to a variety of reasons including atherosclerotic plaque debris distal embolization, lateral branch occlusion, intima exfoliation, and temporary vascular occlusion. Thus, for the PCI cases focusing on the protection of cardiac function, it is important to improve the quality of life of the patients.
Statins, widely used lipid-lowering drugs, are hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that can reduce the plasma lipid protein and cholesterol levels by inhibiting HMG-CoA secretion in liver, thus inhibiting cholesterol biosynthesis. Meanwhile, statins also have definite anti-inflammatory, anti-oxidant, and anti-thrombotic effects, which reduces the stability of atherosclerotic plaques. Therefore, the application of statin before surgery has become the first choice for reducing postoperative MACE in patients with CHD., However, the most common adverse reactions of statins are elevated transaminases which raises the clinical controversial question whether elderly patients can tolerate intensive statin therapy before PCI. In the present study, 105 cases of elderly patients with CHD preoperatively received 20 mg, 40 mg, or 60 mg atorvastatin calcium tablets. We found that the incidence of MACE and PCI-related myocardial infarction was significantly lower in 60 mg group than 20 mg and 40 mg group, as assessed at 1 month after surgery. PCI-related myocardial infarction, mostly induced by transient myocardial ischemia caused by intraoperative balloon dilation, makes it prone to atherosclerotic particulate debris accumulation or blood clots formation in coronary artery. While the anticoagulant or anti-platelet therapies are often unable to effectively inhibit this process, atorvastatin, with its anti-inflammatory and antioxidant property, can improve the vascular endothelial function, besides lipid-regulation, thus playing a positive role in alleviating vascular occlusion caused during transient myocardial ischemia. It effectively reduces the incidence of MACE by reducing the inflammatory reaction around the island of myocardial necrosis. In this study, cardiac markers and hs-CRP levels were found more effectively controlled in 60 mg statin group, agreeing with the above claim.
Vaspin, the adipokine secreted by visceral tissue cells, belongs to the serine protease inhibitor family. In and around the cardiac tissue, vaspin is found expressed in aorta, coronary arteries, and adipose tissues surrounding epicardium. Low vaspin expression has a close association with the development and progression of coronary atherosclerotic plaques. Adiponectin, specifically secreted by the fat cells, mainly engages in collective glucose and lipid metabolism through blood–brain barrier. Meanwhile, adiponectin can exert its anti-inflammatory effect by inducing interleukin-10 secretion, and anti-atherosclerotic effect by promoting tissue inhibitor of metalloproteinase-1 expression. In this study, preoperative vaspin and adiponectin levels in elderly CHD patients were found to be significantly lower than the average level of their healthy counterparts, reflecting its important role in the development of CHD. After intensive statin therapy, the vaspin and adiponectin levels were significantly increased in 60 mg group, suggesting a control in CHD progression to a certain degree. Antonopoulos et al. found that this was also benefited from the strong anti-inflammatory effect of statins. With the exerted anti-inflammatory effects of statins, adiponectin further increases due to the consumption caused by resistance to chronic inflammation, and vaspin is also controlled due to the consumption caused by resistance to endothelial cell apoptosis.
Although ALT in 60 mg statin group significantly increased at 1 month after surgery, its mean value managed to stay within the normal range. Statin-related myopathy did not appear in any of the groups, confirming the positive effect and safety of intensive statin therapy within the assessed duration. However, confined to low sample size and limited follow-up time, the study could not effectively establish the long-term effect and safety of the procedure. In addition, with no control group to compare, changes that exist between presurgical and postsurgical PCI without any treatment could not be explained, which is also a drawback of this study. Overall, the application of 60 mg/day intensive statin therapy in short-term can improve the outcomes of PCI, maintain stable levels of cardiac markers, vaspin and adiponectin levels, with good safety. The efficacy and safety of long-term intensive statin therapy remains to be explored with further studies.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
AIM-HIGH Investigators, Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, McBride R, Teo K, Weintraub W. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med
Dawber TR, Moore FE, Mann GV. II. Coronary heart disease in the Framingham study. Int J Epidemiol
Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, Wiklund O, Hegele RA, Raal FJ, Defesche JC, Wiegman A, Santos RD, Watts GF, Parhofer KG, Hovingh GK, Kovanen PT, Boileau C, Averna M, Borén J, Bruckert E, Catapano AL, Kuivenhoven JA, Pajukanta P, Ray K, Stalenhoef AF, Stroes E, Taskinen MR, Tybjærg-Hansen A; European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: Guidance for clinicians to prevent coronary heart disease: Consensus statement of the European Atherosclerosis Society. Eur Heart J
STABILITY Investigators, White HD, Held C, Stewart R, Tarka E, Brown R, Davies RY, Budaj A, Harrington RA, Steg PG, Ardissino D, Armstrong PW, Avezum A, Aylward PE, Bryce A, Chen H, Chen MF, Corbalan R, Dalby AJ, Danchin N, De Winter RJ, Denchev S, Diaz R, Elisaf M, Flather MD, Goudev AR, Granger CB, Grinfeld L, Hochman JS, Husted S, Kim HS, Koenig W, Linhart A, Lonn E, López-Sendón J, Manolis AJ, Mohler ER 3rd
, Nicolau JC, Pais P, Parkhomenko A, Pedersen TR, Pella D, Ramos-Corrales MA, Ruda M, Sereg M, Siddique S, Sinnaeve P, Smith P, Sritara P, Swart HP, Sy RG, Teramoto T, Tse HF, Watson D, Weaver WD, Weiss R, Viigimaa M, Vinereanu D, Zhu J, Cannon CP, Wallentin L. Darapladib for preventing ischemic events in stable coronary heart disease. N Engl J Med
Wasowicz M, Syed S, Starzyk L, Wijeysundera D, Beattie SW. Abstract 18745: Major adverse cardiac events after non-cardiac surgery following previous percutaneous coronary intervention with stent implantation. Circulation
Kwok CS, Khan MA, Rao SV, Kinnaird T, Sperrin M, Buchan I, de Belder MA, Ludman PF, Nolan J, Loke YK, Mamas MA. Access and non-access site bleeding after percutaneous coronary intervention and risk of subsequent mortality and major adverse cardiovascular events: Systematic review and meta-analysis. Circ Cardiovasc Interv
2015;8(4). pii: e001645.
Kaiser R, Grotemeyer K, Kälsch T, Gräber S, Wilkens H, Elmas E. Decreased TSP-1 following percutaneous coronary intervention is associated with major adverse cardiac events in ST-elevation myocardial infarction. Clin Hemorheol Microcirc
Dimmitt SB, Stampfer HG, Moran A, Scartozzi M, Warren JB. Statin dose based on limited evidence. J Am Coll Cardiol
Nicholls SJ, Ballantyne CM, Barter PJ, Chapman MJ, Erbel RM, Libby P, Raichlen JS, Uno K, Borgman M, Wolski K, Nissen SE. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med
He BX, Shi L, Qiu J, Zeng XH, Zhao SJ. The effect of CYP3A4*1G allele on the pharmacokinetics of atorvastatin in Chinese Han patients with coronary heart disease. J Clin Pharmacol
Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, Wiklund O, Hegele RA, Raal FJ, Defesche JC, Wiegman A, Santos RD, Watts GF, Parhofer KG, Hovingh GK, Kovanen PT, Boileau C, Averna M, Borén J, Bruckert E, Catapano AL, Kuivenhoven JA, Pajukanta P, Ray K, Stalenhoef AF, Stroes E, Taskinen MR, Tybjærg-Hansen A. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: Guidance for clinicians to prevent coronary heart disease: Consensus statement of the European Atherosclerosis Society. Eur Heart J
Preiss D, Lloyd SM, Ford I, McMurray JJ, Holman RR, Welsh P, Fisher M, Packard CJ, Sattar N. Metformin for non-diabetic patients with coronary heart disease (the CAMERA study): A randomised controlled trial. Lancet Diabetes Endocrinol
Rashid H, Khodeer SA, Dastidar AG, Zhu F, Li ZJ, Rong Y, Zhu LX, Yang YL, Wu HS, Luis SA, Raffel OC, Liang Y, Al-Mohammadi M, Blanco JR, Zhuravlyova L, Song HH, Ko B, Caproş N, Hsiung MC, Graham CA, Yan B, Abdel-Moniem A, Email S, El-Batran M, Mansour H, Mahmoud S, Ashour Z, Mustafa S, Abdu-Allah AM, Al-Assal M, Rashid HK, Garg P, West J, Muthusamy R, Gunn J, Lee A, Chee YE, Kang CS, Chen ZY, Zhang YX, Zhao ZX, Song Q, Bao W, Shan ZL, Rong S, Wang D, Yao P, Liu LG, Ho SC, Ruan GQ, Xie Q, Sit JW, Chan MC, Hu M, Chan TY, Tomlinson B, Wang LS, Qin J, Wong TT, Heng PA, Yu CM, Luis CR, Habibian M, Courtney A, Hamilton-Craig C, Strugnell W, Poon K, Slaughter R, Raffel OC, Luis SA, Hansen M, Slaughter R, Hamilton-Craig C, Bai Y, Chen T, Feng GX, Yang YM, Wang XY, Yang YJ, Zhu J, Hersi A, Alhabib KF, Alsheikh-Ali AA, Sulaiman K, Alfaleh H, Alsaif S, Almahmeed W, Asaad N, Amin H, Al-Motarreb A, Al-Suwaid J, Velasco AB, Mancera J, Francisco CA, Lopina N, Xu SH, Huang MZ, Xu CS, Xie LD, Cameron J, Seneviratne S, Leung M, Antonis P, Koutsoubos J, Malaiapan Y, Meredith I, Istrati V, Matcovschi S, Dumitraş T, Istrati S, Nicolenco I, Hotineanu R, Manea D, Gherman O, Ko CH, Wei J, Tung TH, Chan JW, Rotherary KR, Rainer TH, Liu M, Huang XR, Li RJ, Lam YY, Yu CM. Coronary artery disease. Eur Heart J
2012;14 (Suppl A): A14-9.
Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, DeMicco DA, Barter P, Cannon CP, Sabatine MS, Braunwald E, Kastelein JJ, de Lemos JA, Blazing MA, Pedersen TR, Tikkanen MJ, Sattar N, Ray KK. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: A meta-analysis. JAMA
Aronis KN, Moreno M, Polyzos SA, Moreno-Navarrete JM, Ricart W, Delgado E, de la Hera J, Sahin-Efe A, Chamberland JP, Berman R, Spiro A 3rd
, Vokonas P, Fernández-Real JM, Mantzoros CS. Circulating irisin levels and coronary heart disease: Association with future acute coronary syndrome and major adverse cardiovascular events. Int J Obes (Lond)
Armstrong EJ, Chen DC, Westin GG, Singh S, McCoach CE, Bang H, Yeo KK, Anderson D, Amsterdam EA, Laird JR. Adherence to guideline-recommended therapy is associated with decreased major adverse cardiovascular events and major adverse limb events among patients with peripheral arterial disease. J Am Heart Assoc
Cholesterol Treatment Trialists' (CTT) Collaborators, Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, Voysey M, Gray A, Collins R, Baigent C. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: Meta-analysis of individual data from 27 randomised trials. Lancet
Dewilde WJ, Oirbans T, Verheugt FW, Kelder JC, De Smet BJ, Herrman JP, Adriaenssens T, Vrolix M, Heestermans AA, Vis MM, Tijsen JG, van't Hof AW, ten Berg JM; WOEST Study Investigators. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: An open-label, randomised, controlled trial. Lancet
Tikkanen MJ, Fayyad R, Faergeman O, Olsson AG, Wun CC, Laskey R, Kastelein JJ, Holme I, Pedersen TR; IDEAL Investigators. Effect of intensive lipid lowering with atorvastatin on cardiovascular outcomes in coronary heart disease patients with mild-to-moderate baseline elevations in alanine aminotransferase levels. Int J Cardiol
Antonopoulos AS, Margaritis M, Coutinho P, Digby J, Patel R, Psarros C, Ntusi N, Karamitsos TD, Lee R, De Silva R, Petrou M, Sayeed R, Demosthenous M, Bakogiannis C, Wordsworth PB, Tousoulis D, Neubauer S, Channon KM, Antoniades C. Reciprocal effects of systemic inflammation and brain natriuretic peptide on adiponectin biosynthesis in adipose tissue of patients with ischemic heart disease. Arterioscler Thromb Vasc Biol
Antonopoulos AS, Margaritis M, Lee R, Channon K, Antoniades C. Statins as anti-inflammatory agents in atherogenesis: Molecular mechanisms and lessons from the recent clinical trials. Curr Pharm Des
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]