Original research 333
Impact of increased admission lipid levels on periprocedural myocardial injury following an elective percutaneous coronary intervention Ali Buturaka, Aleks Degirmencioglua, Mehmet Erturkc, Hüseyin Karakurtc, Ali Rıza Demirc, Ozgur Surgitc, Hamdi Pusurogluc, Ozgur Akgulc, Mustafa Serteserb, Tugrul Norgaza and Sevket Gorgulua Objective Periprocedural myocardial injury (PMI) is known to be a predictor of in-hospital cardiac events and long-term adverse outcomes following a percutaneous coronary intervention (PCI). We aimed to evaluate the correlation between preprocedural serum lipid levels and PMI in patients undergoing elective PCI.
P < 0.01) between postprocedural hscTnT and lesion length. Mild–moderate PMI (postprocedural hscTnT ≥ 14 to < 70 ng/l) and severe PMI (postprocedural hscTnT ≥ 70 ng/l) were observed in 122 (48.7%) and 27 (13.9%) patients, respectively. The patients with severe PMI had higher serum TC (P < 0.001), LDL-C (P < 0.001), and TG (P < 0.001) concentrations.
Patients and methods The final study group included 195 patients (60.1 ± 0.7 years old, 68 women and 127 men). Serum high-sensitive troponin T (hscTnT) concentrations were measured immediately before PCI and 12 h after PCI. Serum total cholesterol (TC), low-density lipoproteincholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and triglyceride (TG) levels were determined immediately before PCI. Serum hscTnT concentrations were adjusted for the clinical and procedural characteristics of the patients using the weighted least-square regression analysis.
Conclusion The present study indicates that increased preprocedural TC, LDL-C, and TG serum levels are associated with PMI and its severity following elective PCI. Coron Artery Dis 26:333–340 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Results The average preprocedural hscTnT concentration was 8.1 ± 0.2 ng/l. The average serum hscTnT concentration increased to 34.1 ± 2.8 ng/l (P < 0.001) 12 h after PCI. Postprocedural hscTnT concentrations were correlated positively to serum concentrations of TC (r = 0.435; P < 0.001), LDL-C (r = 0.349; P < 0.001), and TG (r = 0.517; P < 0.001). There was also a positive correlation (r = 0.205;
Introduction Percutaneous coronary intervention (PCI) is the main revascularization strategy in patients with ischemic coronary artery disease. Although PCI is safe and associated with low rates of severe complications, periprocedural myocardial injury (PMI) may occur following successful and uneventful PCI procedures [1–7]. High-sensitive troponin assays may detect even minor increases in serum troponin levels that enable us to determine baseline values and even small increases in troponin levels [8]. It is well known that PMI is associated with an increased risk of cardiac events including death during short-term and long-term follow-up [2–5]. Thus, several clinical studies have investigated predictors of PMI and searched for measures to prevent myocardial injury to improve outcomes [7]. To the best of our knowledge, there is no systematic study assessing directly the relationship between preprocedural 0954-6928 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Coronary Artery Disease 2015, 26:333–340 Keywords: high-sensitive troponin, hyperlipidemia, myocardial injury Departments of aCardiology, bMedical Biochemistry, Acibadem University Faculty of Medicine and cCardiology Department, Mehmet Akif Ersoy Cardiovascular Surgery Training and Research Center, Istanbul, Turkey Correspondence to Ali Buturak, MD, Department of Cardiology, Acibadem University Faculty of Medicine, Kerem Aydinlar Kampusu, Icerenkoy Mahallesi Kayisdagi Caddesi No: 32 Atasehir, Istanbul, Turkey Tel: + 90 216 5004444; fax: + 90 216 5765076; e-mail: [email protected] Received 29 November 2014 Revised 13 January 2015 Accepted 26 January 2015
serum lipid status and PMI. Furthermore, available data from indirect studies on the effects of lipid status on PMI are inconsistent and conflicting. Hyperlipidemia was found to be protective in a study that evaluated a risk adjustment model for in-hospital mortality following PCI [9]. Moreover, a previously reported guideline reported a history of hyperlipidemia as a preventive clinical factor against PMI [10]. However, it was reported that the observed benefit in hyperlipidemic patients was because of preprocedural statin therapy rather than hyperlipidemia itself [11]. In contrast, Mandadi et al. [12] reported that PMI is correlated positively with history of hypercholesterolemia in patients either treated or untreated with statins. Higher high-density lipoprotein cholesterol (HDL-C) and lower low-density lipoprotein cholesterol (LDL-C) levels were found to be associated with a lower risk of PMI in two different studies [13,14]. It has also been shown that hyperlipidemia and hypercholesterolemia attenuate the protective action of preconditioning during PCI and DOI: 10.1097/MCA.0000000000000235
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334 Coronary Artery Disease 2015, Vol 26 No 4
prevent the normal reduction of myocardial ischemia on repeated balloon angioplasties [15,16]. This study was designed to assess the relation between preprocedural serum lipid levels and post-intervention high-sensitive troponin T (hscTnT) elevations reflecting PMI following uneventful and successful PCI procedures.
(70–100 IU/kg) was administered before PCI with subsequent bolus doses to maintain an activating clotting time between 250 and 300 s. Predilatation, direct stenting, and postdilatation with a noncompliant balloon were performed according to lesion severity and characteristics. Drug-eluting (everolimus, biolimus, and zotarolimus eluting) and bare metal stents were used for stenting.
Patients and methods
Determination of serum lipid concentrations
Study protocol and population
Peripheral venous blood samples were collected after 10–12 h of fasting and just before PCI. Total cholesterol (TC), LDL-C, HDL-C, and triglyceride (TG) concentrations were measured using an autoanalyzer at the accredited central clinical chemistry laboratory. Patients with serum TC of at least 200 mg/dl, LDL-C of at least 100 mg/dl, and TG of at least 150 mg/dl were defined as the high TC group, the high LDL-C group, and the high TG group, respectively. Patients with serum HDL-C less than 40 mg/dl (in men) or less than 45 mg/dl (in women) were defined as the low HDL-C group.
The present study included 208 patients undergoing elective PCI. Patients presenting with stable angina pectoris and signs of ischemia indicated by either an exercise stress test or myocardial perfusion scintigraphy underwent the procedures. Patients presenting with acute or subacute myocardial infarction, unstable angina pectoris, compensated or decompensated heart failure, chronic renal failure, and a history of chronic inflammatory disease were excluded. Patients with periprocedural anginal symptoms suggestive of myocardial ischemia or new ischemic electrocardiographic changes or new segmentary wall motion abnormality detected by echocardiography were also excluded. In addition, patients with procedure-related complications such as coronary dissection, acute side branch occlusion, or impairment of side branch because of plaque shifting after main vessel stenting or no-reflow were not enrolled. After the first enrollment including 208 patients, eight patients with preprocedural hscTnT concentrations of at least 14 ng/l, two patients with coronary dissection, and three patients with acute side branch occlusion during main vessel stenting were excluded from the study. The final study group included 195 patients with successful and uneventful PCIs. The study was carried out according to the principles of the Declaration of Helsinki and the protocol was approved by the local ethics committee. Each patient provided written informed consent. Coronary lesion morphology classification and percutaneous coronary intervention procedure
Angiograms were acquired using cine-angiographic equipment (Siemens Artis Zee, Forschheim, Germany) in different orthogonal views. The percent diameter stenosis (%) of the coronary lesions was obtained using quantitative coronary angiography software with digital calibration. PCI was performed in patients who had at least one significant coronary artery stenosis amenable to revascularization. Significant stenosis has been defined as at least 70% luminal percent diameter stenosis or 40–69% luminal percent diameter stenosis with fractional flow reserve 0.80 or less in one or more epicardial coronary arteries. Type A, B1, B2, and C lesions were defined as described previously [17]. Standard techniques were performed using femoral or radial approaches. All of the cases were preloaded with 300 mg aspirin and 600 mg clopidogrel before the procedures. Intravenous heparin
Determination of serum high-sensitive troponin T concentrations
Peripheral venous blood samples were collected just before PCI and 12 h after the procedure. Serum supernatant was separated and stored frozen at − 80°C until analysis. Serum troponin T concentration was measured using an hscTnT assay (Elecsys Troponin T-High Sensitive Immunoassay; Roche Diagnostics, Rotkreuz, Switzerland) with an analytical measurement range of 3–1000 ng/l. The assay coefficient of variation was less than 10% at this limit. Determination of periprocedural myocardial injury and myocardial infarction
PMI was defined as described previously [5–7]. Accordingly, we categorized our patients into three groups on the basis of postprocedural serum hscTnT concentrations: (a) noninjury group (patients with serum postprocedural hscTnT concentrations < 14 ng/l); (b) mild–moderate PMI group (patients with ≥ 14 to < 70 ng/l of postprocedural hscTnT concentrations without periprocedural anginal symptoms suggestive of myocardial ischemia or new ischemic electrocardiographic changes or new segmentary wall motion abnormality detected by echocardiography); (c) severe PMI group (patients with ≥ 70 ng/l of postprocedural hscTnT concentrations without periprocedural anginal symptoms suggestive of myocardial ischemia or new ischemic electrocardiographic changes or new segmentary wall motion abnormality detected by echocardiography). Statistical analysis
All analyses were carried out using Sigma Plot 11.0 statistical software (Systat Software Inc., San Jose, California, USA). Continuous variables were reported as mean (± SEM) unless otherwise stated. Two independent
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Hyperlipidemia and PMI Buturak et al. 335
means were compared using a t-test. Preprocedural and postprocedural serum hscTnT concentrations were compared using a paired t-test. For comparison between the three groups, one-way analysis of variance with the posthoc Tukey test was used. Non-normally distributed variables were presented as median (25th–75th percentile) and for comparison between groups, either the Kruskal–Wallis (between three groups) or the Mann–Whitney U-tests (between two groups) were used. For categorical data, χ2 or Fisher exact tests were used where appropriate. Correlations between serum hscTnT concentrations and serum lipid and other parameters were analyzed using the Pearson Product–Moment Correlation analysis. Univariate and multivariate regression analyses were carried out to identify the predictors of the increase in serum hscTnT concentrations. All variables with a P value of less than 0.1 in the univariate analysis were included in the multivariate model. Serum hscTnT concentrations were also adjusted for clinical and procedural characteristics of the patients using the weighted leastsquare regression analysis. A probability value of less than 0.05, with at least 0.80 statistical power, was considered significant.
Results
Demographic and clinical characteristics of the participants
Table 1
Age (mean ± SE) (years) Male [n (%)] Female [n (%)] Smoking [n (%)] Diabetes mellitus [n (%)] Hypertension [n (%)] Previous MI [n (%)] Statin user [n (%)] High-intensity statin pretreatmenta Moderate-intensity statin pretreatmentb β-Adrenoceptor antagonist user [n (%)] ACEI-ARA user [n (%)] LVEF (%) Serum lipids (mean ± SE) (mg/dl) TC LDL-C HDL-C TG Patients with high (≥200 mg/dl) TC [n (%)] Patients with high (≥100 mg/dl) LDL-C [n (%)] Patients with low (< 40 mg/dl) HDL-C [n (%)] Patients with high (≥150 mg/dl) TG [n (%)]
60.1 ± 0.7 127 (65) 68 (35) 49 (25) 74 (38) 138 (71) 45 (23) 90 (46) 42 (47) 48 (53) 129 (66) 118 (61) 62.6 ± 0.4 199 ± 4 123 ± 3 42 ± 2 173 ± 7 66 (34) 89 (46) 90 (46) 100 (51)
ACEI-ARA, angiotensin-converting enzyme inhibitor-angiotensin II receptor antagonist; HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol; LVEF, left ventricular ejection fraction; MI, myocardial infarction; TC, total cholesterol; TG, triglyceride. a High-intensity statin pretreatment indicates atorvastatin 40–80 mg or rosuvastatin 20–40 mg doses/day. b Moderate-intensity statin pretreatment indicates atorvastatin 10–20 mg or rosuvastatin 10 mg doses/day.
Patient characteristics
The study group included 195 patients (60.1 ± 0.7 years old; 68 women and 127 men). Serum TC, LDL-C, and TG concentrations were higher than the target cut-off concentrations in 66 (34%), 89 (46%), and 100 (51%) patients, respectively. Ninety patients were already receiving preprocedural statin therapy either with highintensity or moderate-intensity doses. Forty-two of 90 patients (47%) were receiving high-intensity dose statins before the procedures. Table 1 shows the demographic and clinical characteristics of the patients. Procedural data
The average percent diameter stenosis was 84 ± 1% in the study population. All of the procedures were completed successfully without any procedural failure. Single-vessel PCI was performed in the majority (89%) of the cases. Type C lesion characteristics were present in 105 (54%) participants. Complex bifurcation PCI, ostial coronary PCI, and in-stent restenosis PCI were performed in 17 (8.7%), 16 (8.2%), and 7 (3.5%) patients, respectively. Table 2 shows the procedural data of the study population. High-sensitive troponin concentrations before and after procedures
The average preprocedural hscTnT concentration was 8.1 ± 0.2 ng/l (median: 7.8 ng/l; 25th–75th percentiles: 5.7–11.0 ng/l). The serum hscTnT concentration increased significantly (P < 0.001) to 34.1 ± 2.8 ng/l (median: 20.0 ng/l; 25th–75th percentiles: 12.0–39.7 ng/l) 12 h after the procedures. The average increase (P < 0.001) in the serum hscTnT concentration after the procedures was
Table 2
Procedural characteristics of patients
Procedural success [n (%)] Percent diameter stenosis (mean ± SE) (%) Coronary lesion morphology [n (%)] Type C lesion Type B2 lesion Type B1 lesion Type A lesion Ostial lesion PCI [n (%)] Bifurcation lesion PCI [n (%)] In-stent restenosis PCI [n (%)] Saphenous vein graft PCI [n (%)] Multivessel PCI [n (%)] Single-vessel PCI [n (%)] Predilatation [n (%)] Postdilatation [n (%)] Stent length (mean ± SE) (mm) Stent diameter (mean ± SE) (mm) Drug-eluting stent [n (%)] Bare metal stent [n (%)]
195 (100) 84 ± 1 105 (54) 11 (6) 55 (28) 24 (12) 16 (8.2) 17 (8.5) 7 (3.5) 2 (1) 22 (11) 173 (89) 120 (62) 64 (33) 24.9 ± 1.0 3.03 ± 0.03 111 (57) 84 (43)
PCI, percutaneous coronary intervention.
26.0 ± 2.7 ng/l (median: 11.3 ng/l; 25th–75th percentiles: 3.8–29.4 ng/l). Seventy-three of 195 patients (37.4%) had serum postprocedural hscTnT levels less than 14 ng/l (noninjury group). Postprocedural serum hscTnT levels within the range of 14 and 70 ng/l were observed in 95 patients (48.7%), indicating the mild–moderate PMI group. The severe PMI group included 27 patients (13.8%) with postprocedural hscTnT levels of at least 70 ng/l. The postprocedural serum hscTnT levels were similar in men, women, smokers, in β-blocker or angiotensin-converting
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336 Coronary Artery Disease 2015, Vol 26 No 4
enzyme inhibitor/angiotensin II receptor antagonist users, and in patients with DM or hypertension. The postprocedural serum hscTnT levels were also similar among patients with different lesion types (type A-C, bifurcation, ostial, in-stent restenosis, saphenous venous graft lesions), single-vessel PCI, multivessel PCI, and implantation of drug-eluting or bare metal stents. However, there was a positive correlation (r = 0.205; P < 0.01) between postprocedural serum hsTcT concentrations and stent length, indicating an association between PMI and lesion length. Determinants of postprocedural serum high-sensitive troponin T concentrations
Significant positive correlations (Fig. 1) were observed between postprocedural serum hscTnT concentrations and serum TC (r = 0.435; P < 0.001), LDL-C (r = 0.349; P < 0.001), and TG (r = 0.517; P < 0.001), but not with serum HDL-C (r = − 0.130; P = 0.070). There were also positive correlations between the increase in serum hscTnT concentrations following the procedures and serum TC (r = 0.407; P < 0.001), LDL-C (r = 0.421; P < 0.001), and TG (r = 0.531; P < 0.001). Adjustment of postprocedural hsTnT concentrations for clinical and procedural characteristics of the patients by including sex, smoking, hypertension, diabetes mellitus, use of β-blockers, angiotensin-converting enzyme inhibitor/angiotensin II receptor antagonist users, lesion types, stent types, predilation, postdilation, and multivessel and bifurcation PCI in the weighted least-square regression analysis did not alter the significant association observed between serum lipid parameters and postprocedural serum hscTnT concentrations. Serum high-sensitive troponin T concentrations in patients with low and high serum lipids
Serum hscTnT concentrations in patients with ‘normal’ or ‘high’ serum lipids are shown in Table 3. Postprocedural hscTnT concentrations were significantly higher in the ‘high’ TC, LDL-C, and TG groups than the values observed in ‘normal’ TC, LDL-C, and TG groups (Table 3). Serum postprocedural hscTnT concentrations were similar in both normal and low HDL-C groups (Table 3). Incidences of periprocedural myocardial injury in patient groups with low and high serum lipids
The incidence of PMI in all patient groups with normal or abnormal lipid parameters was similar (Table 4). However, the incidence of severe PMI was significantly higher in high serum TC (27.3%; P < 0.01) or in high serum TG (24.0%; P < 0.001) groups (Table 4). The incidence of severe PMI was also slightly, but not significantly, higher (19.1 vs. 9.4%, P = 0.138) in patients with high serum LDL-C. The incidence of severe PMI was similar in normal and low HDL-C groups (Table 4).
Serum lipid concentrations in noninjury and periprocedural myocardial injury groups
One-way analysis of variance analyses showed that serum TC [F(2,194) = 12.336, P < 0.001], LDL-C [F(2,194) = 7.957, P < 0.001], and TG [F(2,194) = 25 764, P < 0.001] concentrations in patients with severe PMI were significantly higher than the values observed for the mild–moderate PMI and noninjury groups (Table 5). Statistical analysis also showed that serum TC, LDL-C, and TG in patients with mild–moderate PMI were significantly higher (P < 0.001) than the values observed in the noninjury group (Table 5). Serum HDL-C concentrations were not different [F(2,194) = 0.875, P = 0.419] between these three groups (Table 5). Serum lipids and high-sensitive troponin T concentrations in patients using statins
Table 6 summarizes the serum lipid and hscTnT concentrations in statin users and nonusers. Serum TC, LDL-C, TG, and postprocedural hscTnT concentrations were lower in statin users (Table 6). The regression analysis weighted by statin use showed that the model including serum lipid parameters was a significant (r = 0.615; P < 0.001) predictor for postprocedural hscTnT concentrations. Postprocedural hscTnT concentrations were correlated positively with serum TC (r = 0.549; P < 0.001 or r = 0.427; P < 0.001), LDL-C (r = 0.499; P < 0.001 or r = 0.344; P < 0.001) and TG (r = 0.55; P < 0.001 or r = 0.459; P < 0.001) in statin users or nonusers, respectively. Postprocedural hscTnT concentrations also showed a weak negative correlation (r = − 0.209; P < 0.055) with serum HDL-C concentrations in nonusers, but not in statin users (r = 0.076; P = 0.478). In statin users, after adjustment for high-intensity statin pretreatment, serum postprocedural hscTnT concentration maintained its significant correlation with serum TC (r = 0.800; P < 0.001), LDL-C (r = 0.755), and TG (r = 0.810; P 5 times the 99th percentile of the health reference population) in 27 patients, indicating that the incidence of severe PMI was 13.4% in our patient population. In patients with mild–moderate PMI and severe PMI, serum concentrations of TC, LDL-C, and TG were higher than the values observed in the noninjury group. The incidence of severe PMI was significantly higher in patients with high serum TC and TG. Therefore, it is reasonable to suggest that hyperlipidemia increases the risk for PMI and its extent. The mechanism by which hypercholesterolemia and hypertriglyceridemia may influence the severity of myocardial injury
Table 5 Serum lipid status in patients with no periprocedural myocardial injury, mild–moderate periprocedural myocardial injury, and severe periprocedural myocardial injury Serum lipid parameters
No injury (n = 73)
PMI mild–moderate (n = 95)
PMI severe (n = 27)
TC (mg/dl) LDL-C (mg/dl) HDL-C (mg/dl) TG (mg/dl)
163 ± 5 87 ± 5 43 ± 2 142 ± 7
178 ± 5b 102 ± 4b 42 ± 1 167 ± 8b
221 ± 13a 130 ± 13a 39 ± 2 280 ± 26a
Patients with no injury, mild–moderate PMI, and severe PMI groups had serum postprocedural hscTnT concentrations < 14, ≥ 14 to < 70, and ≥ 70 ng/l, respectively. HDL-C, high-density lipoprotein-cholesterol; hscTnT, high-sensitive cardiac troponin T; LDL-C, low-density lipoprotein-cholesterol; PMI, periprocedural myocardial injury; TC, total cholesterol; TG, triglyceride. a Significantly higher than the values obtained from patients with or without myocardial injury (analysis of variance and post-hoc Tukey test). b Significantly higher than the values obtained from patients without myocardial injury (t-test).
Table 6 Serum lipids and high-sensitive cardiac troponin T concentrations in statin users and nonusers
Serum analyses TC (mg/dl) LDL-C (mg/dl) HDL-C (mg/dl) TG (mg/dl) Preprocedural hscTnT (ng/l) Postprocedural hscTnT (ng/l)
Statin users (N = 90)
Nonusers (N = 105)
P*
180 ± 5 108 ± 4 43 ± 1 152 ± 7 7.9 ± 0.4 28.0 ± 2.6
214 ± 5 134 ± 4 42 ± 1 193 ± 11 8.5 ± 0.3 46.0 ± 6.2
< 0.001 < 0.001 0.550 < 0.001 0.211 < 0.05
HDL-C, high-density lipoprotein-cholesterol; hscTnT, high-sensitive cardiac troponin T; LDL-C, low-density lipoprotein-cholesterol; TC, total cholesterol; TG, triglyceride. *P < 0.05 indicates statistically significant differences between statin users and nonusers. The statistical power was > 0.80 in α = 0.05.
induced by PCI is not known. Several mechanisms have been suggested in animal studies such as accumulation of cholesterol in the sarcolemmal and mitochondrial membranes, deterioration of myocardial nitric oxide metabolism, increased formation of reactive oxygen species, attenuation of heat shock response, and significant alterations in gene expressing [20–23]. It could be suggested that the formation and release of endogenous cardioprotective substances may be abolished by hyperlipidemia. In other words, it could also be
Table 4 Incidence of mild–moderate periprocedural myocardial injury and severe periprocedural myocardial injury in patient groups with abnormal serum lipid status Patient lipid groups TC Normal (< 200 mg/dl) High (≥200 mg/dl) LDL-C Normal (< 100 mg/dl) High (≥100 mg/dl) HDL-C Normal (≥40 mg/dl) Low (< 40 mg/dl) TG Normal (< 150 mg/dl) High (≥150 mg/dl)
n
PMI mild–moderate [n (%)]
P
PMI severe [n (%)]
P*
129 66
61 (47.3) 33 (50.0)
0.966
9 (7.0) 18 (27.3)
< 0.01
106 89
50 (47.2) 45 (50.5)
0.880
10 (9.4) 17 (19.1)
0.138
105 90
52 (49.5) 43 (47.8)
0.912
14 (13.3) 13 (14.4)
1.000
95 100
36 (37.9) 48 (48.0)
0.997
3 (3.2) 24 (24.0)
< 0.001
HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol; PMI, periprocedural myocardial injury; TC, total cholesterol; TG, triglyceride. *P < 0.05 indicates a statistically significant difference from the respective values for patients with ‘normal’ lipid status.
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Hyperlipidemia and PMI Buturak et al. 339
hypothesized that the formation and the release of endogenous toxic substances that induce myocardial injury may be enhanced by hyperlipidemia. Clearly, further studies are needed to find the mechanism that may likely be involved in the effect of lipid status on PCI-induced PMI. The significant reduction in postprocedural serum hscTnT concentrations observed in patients under statin treatment was in good agreement with previous studies that show that pretreatment with statins reduces periprocedural myocardial damage and exerts clinical benefits [24–27]. Although the pleiotropic effect of statins by reducing the lipid-rich necrotic core of the plaques is believed to be responsible for cardioprotective and beneficial effects of the preprocedural statin therapy [28], our results support the view that the lipid-lowering action of statins provides additional benefits for cardioprotection during PCI. In the present study, statin users were taking moderate-intensity or high-intensity lipid-lowering doses of statins before procedures and the decrease in the postprocedural serum hscTnT concentration was found to be associated with significantly low serum lipid concentrations. Furthermore, the positive significant association between postprocedural serum hscTnT and serum TC, LDL-C, and TG was evident in both statin users and nonusers. The present study has some limitations. First of all, serum concentrations of postprocedural hscTnT were assessed in blood samples collected only once – 12 h after the PCI. Additional serum hscTnT measurements at the 6th or 24th hours following PCI may provide information on the changes in serum hscTnT concentrations following PCI. Second, we did not assess the relation between serum lipid status, hscTnT concentrations, and shortterm and long-term clinical outcomes of PCI, prospectively. In conclusion, our findings clearly show that increased serum levels of preprocedural TC, LDL-C, and TG are associated with PMI and its extent following elective PCI. Further reductions in serum concentrations of these lipid parameters may provide beneficial effects against myocardial injury or necrosis following elective PCI in daily clinical practice.
Acknowledgements
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Conflicts of interest
There are no conflicts of interest. 19
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Impact of increased admission lipid levels on periprocedural myocardial injury following an elective percutaneous coronary intervention Ali Buturaka, Aleks Degirmencioglua, Mehmet Erturkc, Hüseyin Karakurtc, Ali Rıza Demirc, Ozgur Surgitc, Hamdi Pusurogluc, Ozgur Akgulc, Mustafa Serteserb, Tugrul Norgaza and Sevket Gorgulua Objective Periprocedural myocardial injury (PMI) is known to be a predictor of in-hospital cardiac events and long-term adverse outcomes following a percutaneous coronary intervention (PCI). We aimed to evaluate the correlation between preprocedural serum lipid levels and PMI in patients undergoing elective PCI.
P < 0.01) between postprocedural hscTnT and lesion length. Mild–moderate PMI (postprocedural hscTnT ≥ 14 to < 70 ng/l) and severe PMI (postprocedural hscTnT ≥ 70 ng/l) were observed in 122 (48.7%) and 27 (13.9%) patients, respectively. The patients with severe PMI had higher serum TC (P < 0.001), LDL-C (P < 0.001), and TG (P < 0.001) concentrations.
Patients and methods The final study group included 195 patients (60.1 ± 0.7 years old, 68 women and 127 men). Serum high-sensitive troponin T (hscTnT) concentrations were measured immediately before PCI and 12 h after PCI. Serum total cholesterol (TC), low-density lipoproteincholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and triglyceride (TG) levels were determined immediately before PCI. Serum hscTnT concentrations were adjusted for the clinical and procedural characteristics of the patients using the weighted least-square regression analysis.
Conclusion The present study indicates that increased preprocedural TC, LDL-C, and TG serum levels are associated with PMI and its severity following elective PCI. Coron Artery Dis 26:333–340 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Results The average preprocedural hscTnT concentration was 8.1 ± 0.2 ng/l. The average serum hscTnT concentration increased to 34.1 ± 2.8 ng/l (P < 0.001) 12 h after PCI. Postprocedural hscTnT concentrations were correlated positively to serum concentrations of TC (r = 0.435; P < 0.001), LDL-C (r = 0.349; P < 0.001), and TG (r = 0.517; P < 0.001). There was also a positive correlation (r = 0.205;
Introduction Percutaneous coronary intervention (PCI) is the main revascularization strategy in patients with ischemic coronary artery disease. Although PCI is safe and associated with low rates of severe complications, periprocedural myocardial injury (PMI) may occur following successful and uneventful PCI procedures [1–7]. High-sensitive troponin assays may detect even minor increases in serum troponin levels that enable us to determine baseline values and even small increases in troponin levels [8]. It is well known that PMI is associated with an increased risk of cardiac events including death during short-term and long-term follow-up [2–5]. Thus, several clinical studies have investigated predictors of PMI and searched for measures to prevent myocardial injury to improve outcomes [7]. To the best of our knowledge, there is no systematic study assessing directly the relationship between preprocedural 0954-6928 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Coronary Artery Disease 2015, 26:333–340 Keywords: high-sensitive troponin, hyperlipidemia, myocardial injury Departments of aCardiology, bMedical Biochemistry, Acibadem University Faculty of Medicine and cCardiology Department, Mehmet Akif Ersoy Cardiovascular Surgery Training and Research Center, Istanbul, Turkey Correspondence to Ali Buturak, MD, Department of Cardiology, Acibadem University Faculty of Medicine, Kerem Aydinlar Kampusu, Icerenkoy Mahallesi Kayisdagi Caddesi No: 32 Atasehir, Istanbul, Turkey Tel: + 90 216 5004444; fax: + 90 216 5765076; e-mail: [email protected] Received 29 November 2014 Revised 13 January 2015 Accepted 26 January 2015
serum lipid status and PMI. Furthermore, available data from indirect studies on the effects of lipid status on PMI are inconsistent and conflicting. Hyperlipidemia was found to be protective in a study that evaluated a risk adjustment model for in-hospital mortality following PCI [9]. Moreover, a previously reported guideline reported a history of hyperlipidemia as a preventive clinical factor against PMI [10]. However, it was reported that the observed benefit in hyperlipidemic patients was because of preprocedural statin therapy rather than hyperlipidemia itself [11]. In contrast, Mandadi et al. [12] reported that PMI is correlated positively with history of hypercholesterolemia in patients either treated or untreated with statins. Higher high-density lipoprotein cholesterol (HDL-C) and lower low-density lipoprotein cholesterol (LDL-C) levels were found to be associated with a lower risk of PMI in two different studies [13,14]. It has also been shown that hyperlipidemia and hypercholesterolemia attenuate the protective action of preconditioning during PCI and DOI: 10.1097/MCA.0000000000000235
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334 Coronary Artery Disease 2015, Vol 26 No 4
prevent the normal reduction of myocardial ischemia on repeated balloon angioplasties [15,16]. This study was designed to assess the relation between preprocedural serum lipid levels and post-intervention high-sensitive troponin T (hscTnT) elevations reflecting PMI following uneventful and successful PCI procedures.
(70–100 IU/kg) was administered before PCI with subsequent bolus doses to maintain an activating clotting time between 250 and 300 s. Predilatation, direct stenting, and postdilatation with a noncompliant balloon were performed according to lesion severity and characteristics. Drug-eluting (everolimus, biolimus, and zotarolimus eluting) and bare metal stents were used for stenting.
Patients and methods
Determination of serum lipid concentrations
Study protocol and population
Peripheral venous blood samples were collected after 10–12 h of fasting and just before PCI. Total cholesterol (TC), LDL-C, HDL-C, and triglyceride (TG) concentrations were measured using an autoanalyzer at the accredited central clinical chemistry laboratory. Patients with serum TC of at least 200 mg/dl, LDL-C of at least 100 mg/dl, and TG of at least 150 mg/dl were defined as the high TC group, the high LDL-C group, and the high TG group, respectively. Patients with serum HDL-C less than 40 mg/dl (in men) or less than 45 mg/dl (in women) were defined as the low HDL-C group.
The present study included 208 patients undergoing elective PCI. Patients presenting with stable angina pectoris and signs of ischemia indicated by either an exercise stress test or myocardial perfusion scintigraphy underwent the procedures. Patients presenting with acute or subacute myocardial infarction, unstable angina pectoris, compensated or decompensated heart failure, chronic renal failure, and a history of chronic inflammatory disease were excluded. Patients with periprocedural anginal symptoms suggestive of myocardial ischemia or new ischemic electrocardiographic changes or new segmentary wall motion abnormality detected by echocardiography were also excluded. In addition, patients with procedure-related complications such as coronary dissection, acute side branch occlusion, or impairment of side branch because of plaque shifting after main vessel stenting or no-reflow were not enrolled. After the first enrollment including 208 patients, eight patients with preprocedural hscTnT concentrations of at least 14 ng/l, two patients with coronary dissection, and three patients with acute side branch occlusion during main vessel stenting were excluded from the study. The final study group included 195 patients with successful and uneventful PCIs. The study was carried out according to the principles of the Declaration of Helsinki and the protocol was approved by the local ethics committee. Each patient provided written informed consent. Coronary lesion morphology classification and percutaneous coronary intervention procedure
Angiograms were acquired using cine-angiographic equipment (Siemens Artis Zee, Forschheim, Germany) in different orthogonal views. The percent diameter stenosis (%) of the coronary lesions was obtained using quantitative coronary angiography software with digital calibration. PCI was performed in patients who had at least one significant coronary artery stenosis amenable to revascularization. Significant stenosis has been defined as at least 70% luminal percent diameter stenosis or 40–69% luminal percent diameter stenosis with fractional flow reserve 0.80 or less in one or more epicardial coronary arteries. Type A, B1, B2, and C lesions were defined as described previously [17]. Standard techniques were performed using femoral or radial approaches. All of the cases were preloaded with 300 mg aspirin and 600 mg clopidogrel before the procedures. Intravenous heparin
Determination of serum high-sensitive troponin T concentrations
Peripheral venous blood samples were collected just before PCI and 12 h after the procedure. Serum supernatant was separated and stored frozen at − 80°C until analysis. Serum troponin T concentration was measured using an hscTnT assay (Elecsys Troponin T-High Sensitive Immunoassay; Roche Diagnostics, Rotkreuz, Switzerland) with an analytical measurement range of 3–1000 ng/l. The assay coefficient of variation was less than 10% at this limit. Determination of periprocedural myocardial injury and myocardial infarction
PMI was defined as described previously [5–7]. Accordingly, we categorized our patients into three groups on the basis of postprocedural serum hscTnT concentrations: (a) noninjury group (patients with serum postprocedural hscTnT concentrations < 14 ng/l); (b) mild–moderate PMI group (patients with ≥ 14 to < 70 ng/l of postprocedural hscTnT concentrations without periprocedural anginal symptoms suggestive of myocardial ischemia or new ischemic electrocardiographic changes or new segmentary wall motion abnormality detected by echocardiography); (c) severe PMI group (patients with ≥ 70 ng/l of postprocedural hscTnT concentrations without periprocedural anginal symptoms suggestive of myocardial ischemia or new ischemic electrocardiographic changes or new segmentary wall motion abnormality detected by echocardiography). Statistical analysis
All analyses were carried out using Sigma Plot 11.0 statistical software (Systat Software Inc., San Jose, California, USA). Continuous variables were reported as mean (± SEM) unless otherwise stated. Two independent
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Hyperlipidemia and PMI Buturak et al. 335
means were compared using a t-test. Preprocedural and postprocedural serum hscTnT concentrations were compared using a paired t-test. For comparison between the three groups, one-way analysis of variance with the posthoc Tukey test was used. Non-normally distributed variables were presented as median (25th–75th percentile) and for comparison between groups, either the Kruskal–Wallis (between three groups) or the Mann–Whitney U-tests (between two groups) were used. For categorical data, χ2 or Fisher exact tests were used where appropriate. Correlations between serum hscTnT concentrations and serum lipid and other parameters were analyzed using the Pearson Product–Moment Correlation analysis. Univariate and multivariate regression analyses were carried out to identify the predictors of the increase in serum hscTnT concentrations. All variables with a P value of less than 0.1 in the univariate analysis were included in the multivariate model. Serum hscTnT concentrations were also adjusted for clinical and procedural characteristics of the patients using the weighted leastsquare regression analysis. A probability value of less than 0.05, with at least 0.80 statistical power, was considered significant.
Results
Demographic and clinical characteristics of the participants
Table 1
Age (mean ± SE) (years) Male [n (%)] Female [n (%)] Smoking [n (%)] Diabetes mellitus [n (%)] Hypertension [n (%)] Previous MI [n (%)] Statin user [n (%)] High-intensity statin pretreatmenta Moderate-intensity statin pretreatmentb β-Adrenoceptor antagonist user [n (%)] ACEI-ARA user [n (%)] LVEF (%) Serum lipids (mean ± SE) (mg/dl) TC LDL-C HDL-C TG Patients with high (≥200 mg/dl) TC [n (%)] Patients with high (≥100 mg/dl) LDL-C [n (%)] Patients with low (< 40 mg/dl) HDL-C [n (%)] Patients with high (≥150 mg/dl) TG [n (%)]
60.1 ± 0.7 127 (65) 68 (35) 49 (25) 74 (38) 138 (71) 45 (23) 90 (46) 42 (47) 48 (53) 129 (66) 118 (61) 62.6 ± 0.4 199 ± 4 123 ± 3 42 ± 2 173 ± 7 66 (34) 89 (46) 90 (46) 100 (51)
ACEI-ARA, angiotensin-converting enzyme inhibitor-angiotensin II receptor antagonist; HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol; LVEF, left ventricular ejection fraction; MI, myocardial infarction; TC, total cholesterol; TG, triglyceride. a High-intensity statin pretreatment indicates atorvastatin 40–80 mg or rosuvastatin 20–40 mg doses/day. b Moderate-intensity statin pretreatment indicates atorvastatin 10–20 mg or rosuvastatin 10 mg doses/day.
Patient characteristics
The study group included 195 patients (60.1 ± 0.7 years old; 68 women and 127 men). Serum TC, LDL-C, and TG concentrations were higher than the target cut-off concentrations in 66 (34%), 89 (46%), and 100 (51%) patients, respectively. Ninety patients were already receiving preprocedural statin therapy either with highintensity or moderate-intensity doses. Forty-two of 90 patients (47%) were receiving high-intensity dose statins before the procedures. Table 1 shows the demographic and clinical characteristics of the patients. Procedural data
The average percent diameter stenosis was 84 ± 1% in the study population. All of the procedures were completed successfully without any procedural failure. Single-vessel PCI was performed in the majority (89%) of the cases. Type C lesion characteristics were present in 105 (54%) participants. Complex bifurcation PCI, ostial coronary PCI, and in-stent restenosis PCI were performed in 17 (8.7%), 16 (8.2%), and 7 (3.5%) patients, respectively. Table 2 shows the procedural data of the study population. High-sensitive troponin concentrations before and after procedures
The average preprocedural hscTnT concentration was 8.1 ± 0.2 ng/l (median: 7.8 ng/l; 25th–75th percentiles: 5.7–11.0 ng/l). The serum hscTnT concentration increased significantly (P < 0.001) to 34.1 ± 2.8 ng/l (median: 20.0 ng/l; 25th–75th percentiles: 12.0–39.7 ng/l) 12 h after the procedures. The average increase (P < 0.001) in the serum hscTnT concentration after the procedures was
Table 2
Procedural characteristics of patients
Procedural success [n (%)] Percent diameter stenosis (mean ± SE) (%) Coronary lesion morphology [n (%)] Type C lesion Type B2 lesion Type B1 lesion Type A lesion Ostial lesion PCI [n (%)] Bifurcation lesion PCI [n (%)] In-stent restenosis PCI [n (%)] Saphenous vein graft PCI [n (%)] Multivessel PCI [n (%)] Single-vessel PCI [n (%)] Predilatation [n (%)] Postdilatation [n (%)] Stent length (mean ± SE) (mm) Stent diameter (mean ± SE) (mm) Drug-eluting stent [n (%)] Bare metal stent [n (%)]
195 (100) 84 ± 1 105 (54) 11 (6) 55 (28) 24 (12) 16 (8.2) 17 (8.5) 7 (3.5) 2 (1) 22 (11) 173 (89) 120 (62) 64 (33) 24.9 ± 1.0 3.03 ± 0.03 111 (57) 84 (43)
PCI, percutaneous coronary intervention.
26.0 ± 2.7 ng/l (median: 11.3 ng/l; 25th–75th percentiles: 3.8–29.4 ng/l). Seventy-three of 195 patients (37.4%) had serum postprocedural hscTnT levels less than 14 ng/l (noninjury group). Postprocedural serum hscTnT levels within the range of 14 and 70 ng/l were observed in 95 patients (48.7%), indicating the mild–moderate PMI group. The severe PMI group included 27 patients (13.8%) with postprocedural hscTnT levels of at least 70 ng/l. The postprocedural serum hscTnT levels were similar in men, women, smokers, in β-blocker or angiotensin-converting
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336 Coronary Artery Disease 2015, Vol 26 No 4
enzyme inhibitor/angiotensin II receptor antagonist users, and in patients with DM or hypertension. The postprocedural serum hscTnT levels were also similar among patients with different lesion types (type A-C, bifurcation, ostial, in-stent restenosis, saphenous venous graft lesions), single-vessel PCI, multivessel PCI, and implantation of drug-eluting or bare metal stents. However, there was a positive correlation (r = 0.205; P < 0.01) between postprocedural serum hsTcT concentrations and stent length, indicating an association between PMI and lesion length. Determinants of postprocedural serum high-sensitive troponin T concentrations
Significant positive correlations (Fig. 1) were observed between postprocedural serum hscTnT concentrations and serum TC (r = 0.435; P < 0.001), LDL-C (r = 0.349; P < 0.001), and TG (r = 0.517; P < 0.001), but not with serum HDL-C (r = − 0.130; P = 0.070). There were also positive correlations between the increase in serum hscTnT concentrations following the procedures and serum TC (r = 0.407; P < 0.001), LDL-C (r = 0.421; P < 0.001), and TG (r = 0.531; P < 0.001). Adjustment of postprocedural hsTnT concentrations for clinical and procedural characteristics of the patients by including sex, smoking, hypertension, diabetes mellitus, use of β-blockers, angiotensin-converting enzyme inhibitor/angiotensin II receptor antagonist users, lesion types, stent types, predilation, postdilation, and multivessel and bifurcation PCI in the weighted least-square regression analysis did not alter the significant association observed between serum lipid parameters and postprocedural serum hscTnT concentrations. Serum high-sensitive troponin T concentrations in patients with low and high serum lipids
Serum hscTnT concentrations in patients with ‘normal’ or ‘high’ serum lipids are shown in Table 3. Postprocedural hscTnT concentrations were significantly higher in the ‘high’ TC, LDL-C, and TG groups than the values observed in ‘normal’ TC, LDL-C, and TG groups (Table 3). Serum postprocedural hscTnT concentrations were similar in both normal and low HDL-C groups (Table 3). Incidences of periprocedural myocardial injury in patient groups with low and high serum lipids
The incidence of PMI in all patient groups with normal or abnormal lipid parameters was similar (Table 4). However, the incidence of severe PMI was significantly higher in high serum TC (27.3%; P < 0.01) or in high serum TG (24.0%; P < 0.001) groups (Table 4). The incidence of severe PMI was also slightly, but not significantly, higher (19.1 vs. 9.4%, P = 0.138) in patients with high serum LDL-C. The incidence of severe PMI was similar in normal and low HDL-C groups (Table 4).
Serum lipid concentrations in noninjury and periprocedural myocardial injury groups
One-way analysis of variance analyses showed that serum TC [F(2,194) = 12.336, P < 0.001], LDL-C [F(2,194) = 7.957, P < 0.001], and TG [F(2,194) = 25 764, P < 0.001] concentrations in patients with severe PMI were significantly higher than the values observed for the mild–moderate PMI and noninjury groups (Table 5). Statistical analysis also showed that serum TC, LDL-C, and TG in patients with mild–moderate PMI were significantly higher (P < 0.001) than the values observed in the noninjury group (Table 5). Serum HDL-C concentrations were not different [F(2,194) = 0.875, P = 0.419] between these three groups (Table 5). Serum lipids and high-sensitive troponin T concentrations in patients using statins
Table 6 summarizes the serum lipid and hscTnT concentrations in statin users and nonusers. Serum TC, LDL-C, TG, and postprocedural hscTnT concentrations were lower in statin users (Table 6). The regression analysis weighted by statin use showed that the model including serum lipid parameters was a significant (r = 0.615; P < 0.001) predictor for postprocedural hscTnT concentrations. Postprocedural hscTnT concentrations were correlated positively with serum TC (r = 0.549; P < 0.001 or r = 0.427; P < 0.001), LDL-C (r = 0.499; P < 0.001 or r = 0.344; P < 0.001) and TG (r = 0.55; P < 0.001 or r = 0.459; P < 0.001) in statin users or nonusers, respectively. Postprocedural hscTnT concentrations also showed a weak negative correlation (r = − 0.209; P < 0.055) with serum HDL-C concentrations in nonusers, but not in statin users (r = 0.076; P = 0.478). In statin users, after adjustment for high-intensity statin pretreatment, serum postprocedural hscTnT concentration maintained its significant correlation with serum TC (r = 0.800; P < 0.001), LDL-C (r = 0.755), and TG (r = 0.810; P 5 times the 99th percentile of the health reference population) in 27 patients, indicating that the incidence of severe PMI was 13.4% in our patient population. In patients with mild–moderate PMI and severe PMI, serum concentrations of TC, LDL-C, and TG were higher than the values observed in the noninjury group. The incidence of severe PMI was significantly higher in patients with high serum TC and TG. Therefore, it is reasonable to suggest that hyperlipidemia increases the risk for PMI and its extent. The mechanism by which hypercholesterolemia and hypertriglyceridemia may influence the severity of myocardial injury
Table 5 Serum lipid status in patients with no periprocedural myocardial injury, mild–moderate periprocedural myocardial injury, and severe periprocedural myocardial injury Serum lipid parameters
No injury (n = 73)
PMI mild–moderate (n = 95)
PMI severe (n = 27)
TC (mg/dl) LDL-C (mg/dl) HDL-C (mg/dl) TG (mg/dl)
163 ± 5 87 ± 5 43 ± 2 142 ± 7
178 ± 5b 102 ± 4b 42 ± 1 167 ± 8b
221 ± 13a 130 ± 13a 39 ± 2 280 ± 26a
Patients with no injury, mild–moderate PMI, and severe PMI groups had serum postprocedural hscTnT concentrations < 14, ≥ 14 to < 70, and ≥ 70 ng/l, respectively. HDL-C, high-density lipoprotein-cholesterol; hscTnT, high-sensitive cardiac troponin T; LDL-C, low-density lipoprotein-cholesterol; PMI, periprocedural myocardial injury; TC, total cholesterol; TG, triglyceride. a Significantly higher than the values obtained from patients with or without myocardial injury (analysis of variance and post-hoc Tukey test). b Significantly higher than the values obtained from patients without myocardial injury (t-test).
Table 6 Serum lipids and high-sensitive cardiac troponin T concentrations in statin users and nonusers
Serum analyses TC (mg/dl) LDL-C (mg/dl) HDL-C (mg/dl) TG (mg/dl) Preprocedural hscTnT (ng/l) Postprocedural hscTnT (ng/l)
Statin users (N = 90)
Nonusers (N = 105)
P*
180 ± 5 108 ± 4 43 ± 1 152 ± 7 7.9 ± 0.4 28.0 ± 2.6
214 ± 5 134 ± 4 42 ± 1 193 ± 11 8.5 ± 0.3 46.0 ± 6.2
< 0.001 < 0.001 0.550 < 0.001 0.211 < 0.05
HDL-C, high-density lipoprotein-cholesterol; hscTnT, high-sensitive cardiac troponin T; LDL-C, low-density lipoprotein-cholesterol; TC, total cholesterol; TG, triglyceride. *P < 0.05 indicates statistically significant differences between statin users and nonusers. The statistical power was > 0.80 in α = 0.05.
induced by PCI is not known. Several mechanisms have been suggested in animal studies such as accumulation of cholesterol in the sarcolemmal and mitochondrial membranes, deterioration of myocardial nitric oxide metabolism, increased formation of reactive oxygen species, attenuation of heat shock response, and significant alterations in gene expressing [20–23]. It could be suggested that the formation and release of endogenous cardioprotective substances may be abolished by hyperlipidemia. In other words, it could also be
Table 4 Incidence of mild–moderate periprocedural myocardial injury and severe periprocedural myocardial injury in patient groups with abnormal serum lipid status Patient lipid groups TC Normal (< 200 mg/dl) High (≥200 mg/dl) LDL-C Normal (< 100 mg/dl) High (≥100 mg/dl) HDL-C Normal (≥40 mg/dl) Low (< 40 mg/dl) TG Normal (< 150 mg/dl) High (≥150 mg/dl)
n
PMI mild–moderate [n (%)]
P
PMI severe [n (%)]
P*
129 66
61 (47.3) 33 (50.0)
0.966
9 (7.0) 18 (27.3)
< 0.01
106 89
50 (47.2) 45 (50.5)
0.880
10 (9.4) 17 (19.1)
0.138
105 90
52 (49.5) 43 (47.8)
0.912
14 (13.3) 13 (14.4)
1.000
95 100
36 (37.9) 48 (48.0)
0.997
3 (3.2) 24 (24.0)
< 0.001
HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol; PMI, periprocedural myocardial injury; TC, total cholesterol; TG, triglyceride. *P < 0.05 indicates a statistically significant difference from the respective values for patients with ‘normal’ lipid status.
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Hyperlipidemia and PMI Buturak et al. 339
hypothesized that the formation and the release of endogenous toxic substances that induce myocardial injury may be enhanced by hyperlipidemia. Clearly, further studies are needed to find the mechanism that may likely be involved in the effect of lipid status on PCI-induced PMI. The significant reduction in postprocedural serum hscTnT concentrations observed in patients under statin treatment was in good agreement with previous studies that show that pretreatment with statins reduces periprocedural myocardial damage and exerts clinical benefits [24–27]. Although the pleiotropic effect of statins by reducing the lipid-rich necrotic core of the plaques is believed to be responsible for cardioprotective and beneficial effects of the preprocedural statin therapy [28], our results support the view that the lipid-lowering action of statins provides additional benefits for cardioprotection during PCI. In the present study, statin users were taking moderate-intensity or high-intensity lipid-lowering doses of statins before procedures and the decrease in the postprocedural serum hscTnT concentration was found to be associated with significantly low serum lipid concentrations. Furthermore, the positive significant association between postprocedural serum hscTnT and serum TC, LDL-C, and TG was evident in both statin users and nonusers. The present study has some limitations. First of all, serum concentrations of postprocedural hscTnT were assessed in blood samples collected only once – 12 h after the PCI. Additional serum hscTnT measurements at the 6th or 24th hours following PCI may provide information on the changes in serum hscTnT concentrations following PCI. Second, we did not assess the relation between serum lipid status, hscTnT concentrations, and shortterm and long-term clinical outcomes of PCI, prospectively. In conclusion, our findings clearly show that increased serum levels of preprocedural TC, LDL-C, and TG are associated with PMI and its extent following elective PCI. Further reductions in serum concentrations of these lipid parameters may provide beneficial effects against myocardial injury or necrosis following elective PCI in daily clinical practice.
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Conflicts of interest
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