Abstract
Background
Lipid-lowering therapy plays an important role in preventing the recurrence of cardiovascular events in patients after acute myocardial infarction (AMI). This study aimed to assess the effect of intensified low density lipoprotein cholesterol (LDL-C) reduction on recurrent myocardial infarction and cardiovascular mortality in patients after AMI.
Method
The 562 enrolled AMI patients (84.2% male) were divided into two groups according to 3-month LDL-C decrease percentage equal to or more than 40% (n = 165) and less than 40% (n = 397). To evaluate the long-term efficacy of LDL-C reduction, the 5-year outcomes were collected, including time to the first occurrence of myocardial infarction and time to cardiovascular death.
Results
The baseline characteristics and complication rates were not different between the two study groups. The patients with 3-month LDL-C decrease ≥ 40% had higher baseline LDL-C and lower 3-month, 1-year, 2-year, 3-year, 4-year and 5-year LDL-C than the patients with 3-month LDL-C decrease < 40%. In Kaplan-Meier analyses, those patients with 3-month LDL-C decrease ≥ 40% had a higher rate of freedom from myocardial infarction (p = 0.006) and survival rate (p = 0.02) at 5-year follow-up. The 3-month LDL-C < 40% parameter was significantly related to cardiovascular death (HR: 9.62, 95% CI 1.18-78.62, p < 0.04).
Conclusions
After acute myocardial infarction, 3-month LDL-C decrease < 40% was identified to be a significant risk factor for predicting 5-year cardiovascular death. The patients with 3-month LDL-C decrease ≥ 40% had a higher rate of freedom from myocardial infarction and lower cardiovascular mortality, even though these patients had higher baseline LDL-C value.
Keywords: Acute myocardial infarction, Cardiovascular death, Low-density lipoprotein cholesterol, Mortality, Statin
INTRODUCTION
Acute myocardial infarction (AMI) is one of the major causes of morbidity and mortality in Taiwan and worldwide.1-3 Furthermore, assessing the risk factor of clinical outcomes after AMI remains an important research topic.4-11 Elevated serum levels of low-density lipoprotein cholesterol (LDL-C), a well-known risk factor for development and progression of coronary artery disease, contributes destabilization of atherosclerotic vascular disease and further significantly increases the risk of AMI.12-14 Lipid-lowering therapy plays a critical role in preventing the recurrence of cardiovascular events in primary or secondary prevention. Previous studies have demonstrated that lowering LDL-C levels with statins reduces the risk of recurrent cardiovascular events and improve survival in patients with AMI.15-21
National Cholesterol Education Program (NCEP) guidelines recommend that intensity of therapy should be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels in high risk individuals.22 Earlier studies in patients with stable angina showed that a significant positive correlation was identified between the percentage reduction in LDL-C during the first 3 months after coronary revascularization and the time until recurrence of cardiovascular events.23 However, no prior publication compared the outcomes of reducing LDL-C ≥ 40% and less than 40% in patients with AMI. Therefore, the aim of this study was to assess the effect of intensified LDL-C reduction on recurrent myocardial infarction and cardiovascular mortality in patients after AMI.
MATERIALS AND METHODS
Patients
A total of 661 consecutive patients diagnosed with acute myocardial infarction were enrolled in this study from Jan. 2005 to Dec. 2007. Diagnosis of AMI was made on the basis of typical angina lasting more than 30 minutes, new electrocardiographic change that included ST-segment elevation 0.2 mV in 2 contiguous electrocardiographic leads or other ST/T changes, biochemical evidence of peak creatine kinase more than 2 times the upper limit of normal, and wall motion abnormalities by echocardiography.4,10,11 Criteria for exclusion were patients with LDL-C less than 70 mg/dl, loss follow-up and a diagnosis of chronic hepatitis or cirrhosis. Therefore, a total of 562 patients were included in the study. The Human Research Committee of our hospital approved the study protocol.
Data collection
The basic data was collected, including hypertension, diabetes mellitus, smoking history, uremia, chronic obstructive pulmonary disease, gout, family history of coronary artery disease and Killip class. The previous stroke or myocardial infarction events were also collected.
The vital signs, such as heart rate, systolic and diastolic blood pressure, were measured at the emergency department and discharge. The peripheral blood samples were drawn at the emergency room or after admission, including peak creatinine kinase (CK), CK-MB isoform, Troponin I, creatinine, total bilirubin and alanine aminotransferase. Serum total cholesterol, LDL-C, high density lipoprotein-cholesterol (HDL-C) and triglycerides were checked at fasting status. Three months after discharge, all patients received follow-up blood sampling, including creatinine, total bilirubin, alanine aminotransferase, total cholesterol, LDL-C, HDL-C and triglyceride.
The following complications were also recorded, including: cardiogenic shock, complete atrioventricular block, use of intra-aortic balloon pump, use of temporal pacemaker, ventricular septal defect, mitral regurgitation, ventricular tachycardia, ventricular fibrillation, atrial fibrillation, use of mechanical ventilator and post cardiopulmonary resuscitation.
Medication
All patients with AMI received aspirin 300 mg and clopidogrel 300 mg at the emergency room. Then, heparin, glycoprotein IIb/IIIa inhibitor and beta-blocker were prescribed if no contraindication. After admission, aspirin, clopidogrel, beta-blocker, angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blocker (ARB) were prescribed if patients had no contraindication. The choice of statin use was dependent on the decision of attending physicians. Additionally. the medications administered at the emergency room and discharge were recorded.
Clinical evaluation and outcomes
To evaluate the long-term efficacy of LDL-C reduction, the 5-year outcomes were collected, including time to the first occurrence of myocardial infarction and time to cardiovascular death.
Statistics
The data were analyzed statistically at p < 0.05 using SPSS version 21.0 (SPSS Inc, Chicago, IL, USA). The continuous data was shown as mean and standard deviation and the categorical data was shown as percentages. An independent t test was used for continuous variables and a Chi-square test was used to analysis categorical variables. Kaplan-Meier analyses were used to assess long term survival and freedom from myocardial infarction. The relations of LDL-C variables with cardiovascular mortality were examined using multivariable Cox proportional hazards regression.
RESULTS
Baseline characteristics (Table 1)
Table 1. Baseline characteristics of two study groups.
| 3 month LDL-C decrease ≥ 40% | 3 month LDL-C decrease < 40% | ||
| (Group 1) N = 165 | (Group 2) N = 397 | p value | |
| Male | 140 (84.8%) | 333 (83.9%) | 0.9 |
| Age | 60.3 ± 13.3 | 61.3 ± 13.6 | 0.43 |
| Body weight (kg) | 81.0 ± 13.0 | 68.4 ± 13.8 | 0.05 |
| Body height (cm) | 164.8 ± 8.0 | 163.8 ± 16.2 | 0.58 |
| Current smoker | 80 (48.5%) | 179 (45.1%) | 0.52 |
| Ex-smoker | 23 (13.9%) | 68 (17.1%) | 0.38 |
| Underlying diseases | |||
| Hypertension | 92 (58.2%) | 230 (57.9%) | 0.64 |
| Diabetes | 59 (37.6%) | 150 (37.8%) | 0.63 |
| Uremia | 2 (1.2%) | 6 (1.5%) | 1 |
| COPD | 6 (3.6%) | 12 (3.0%) | 0.79 |
| Previous infarction | 7 (4.2%) | 28 (7.1%) | 0.25 |
| Previous stroke | 10 (14.9%) | 22 (14.4%) | 1 |
| Family history of CAD | 21 (12.7%) | 40 (10.1%) | 0.37 |
| Gout | 13 (7.9%) | 27 (6.8%) | 0.72 |
| Menopause | 6 (3.6%) | 21 (5.3%) | 0.52 |
| Killip class | 1.8 ± 1.0 | 1.8 ± 1.0 | 0.98 |
| Hospital stay (days) | 7.9 ± 7.0 | 9.7 ± 9.4 | 0.26 |
| Vital sign at emergent department | |||
| Heart rate (beats/minute) | 81.2 ± 24.9 | 81.1 ± 25.6 | 0.96 |
| SBP (mmHg) | 139.7 ± 40.4 | 138.5 ± 53.4 | 0.8 |
| DBP (mmHg) | 80.5 ± 29.3 | 75.2 ± 30.8 | 0.07 |
| Vital sign at discharge | |||
| Heart rate (beats/minute) | 67.4 ± 24.3 | 68.6 ± 25.0 | 0.6 |
| SBP (mmHg) | 117.7 ± 22.6 | 117.7 ± 20.7 | 0.99 |
| DBP (mmHg) | 64.4 ± 26.2 | 61.7 ± 29.7 | 0.31 |
CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; DBP, diastolic blood pressure; LDL-C, low density lipoprotein-cholesterol; SBP: systolic blood pressure.
The patients (n = 562, 84.2% male) were divided into two groups according to whether the 3-month LDL-C decrease percentage was equal to or more than 40% (n = 165), or less than 40% (n = 397). The patients with 3-month LDL-C decrease ≥ 40% (group 1, n = 165) had similar age with those patients with 3-month LDL decrease < 40% (group 2, n = 397) (60.3 ± 13.3 vs. 61.3 ± 13.6, p = 0.43). The patients in group 1 were heavier than group 2 patients, although not significantly (81.0 ± 13.0 vs. 68.4 ± 13.8, p = 0.05). There were no differences between the two groups in body height, percentage of smoker, hypertension, diabetes, uremia, chronic obstructive pulmonary disease, previous infarction, previous stoke, family history of coronary artery disease and gout. The severity of AMI, shown as Killip Class, was not different between the 2 groups (1.8 ± 1.0 vs. 1.8 ± 1.0, p = 0.98). There was also no difference between the two groups in both length of hospital stay and vital signs at the emergency department or discharge.
Complication rates
Whether the patients with 3-month LDL-C decrease ≥ 40% or < 40%, the 2 groups had similar complication rates, including cardiogenic shock, complete atrioventricular block, ventricular septal defect, mitral regurgitation, ventricular tachycardia, ventricular fibrillation, atrial fibrillation and post cardiopulmonary resuscitation. There was also no difference in use of mechanical ventilator, intra-aortic balloon pump and temporal pacemaker between the 2 groups.
Laboratory data (Table 2)
Table 2. Complication rates and laboratory data of two study groups.
| 3 month LDL-C decrease ≥ 40% | 3 month LDL-C decrease < 40% | ||
| (Group 1) N = 165 | (Group 2) N = 397 | p value | |
| Complication rates | |||
| Cardiogenic shock | 16 (9.7%) | 40 (10.1%) | 1 |
| Post IABP | 6 (3.6%) | 21 (5.3%) | 0.52 |
| CAVB | 3 (1.8%) | 10 (2.5%) | 0.77 |
| Post temporal pacemaker | 2 (1.2%) | 12 (3.0%) | 0.37 |
| Ventricular septal defect | |||
| Mitral regurgitation | 3 (1.8%) | 10 (2.5%) | 0.77 |
| Ventricular tachycardia | 5 (3.0%) | 11 (2.8%) | 1 |
| Ventricular fibrillation | 5 (3.0%) | 6 (1.5%) | 0.31 |
| Atrial fibrillation | 3 (1.8%) | 9 (2.3%) | 1 |
| Post mechanical ventilator | 12 (7.3%) | 30 (7.6%) | 1 |
| Post cardiopulmonary resuscitation | 2 (1.2%) | 5 (1.3%) | 1 |
| Laboratory data | |||
| Peak CK (U/L) | 2605.7 ± 2558.9 | 2400.0 ± 2568.7 | 0.4 |
| Peak CK-MB(U/L) | 223.0 ± 204.3 | 200.4 ± 216.7 | 0.27 |
| Peak Troponin I (mg/dL) | 112.3 ± 133.7 | 117.4 ± 155.1 | 0.7 |
| Creatinine (mg/dL) | 1.2 ± 1.1 | 1.3 ± 1.2 | 0.37 |
| Total bilirubin (mg/dL) | 0.8 ± 0.3 | 0.8 ± 0.4 | 0.81 |
| GPT (U/L) | 43.5 ± 31.7 | 49.5 ± 116.5 | 0.53 |
| Total cholesterol (mg/dL) | 204.2 ± 40.7 | 177.7 ± 44.1 | < 0.001 |
| HDL-C (mg/dL) | 37.7 ± 9.7 | 36 ± 9.3 | 0.046 |
| LDL-C (mg/dL) | 129.6 ± 29.3 | 109.8 ± 28.9 | < 0.001 |
| Triglyceride (mg/dL) | 121.6 ± 129.2 | 121.2 ± 87.6 | 0.97 |
CAVB, complete atrioventricular block; CK, creatinine kinase; GPT, alanine aminotransferase; HDL-C, high density lipoprotein-cholesterol; IABP, intra aortic balloon pump; LDL-C, low density lipoprotein-cholesterol.
There were no significant differences in peak creatinine kinase, peak CK-MB isoform, peak Troponin I, creatinine, total bilirubin and alanine aminotransferase between the 2 groups. In the lipid profile, the patients with 3-month LDL-C decrease ≥ 40% had higher baseline total cholesterol (204.2 ± 40.7 vs. 177.7 ± 44.1, p < 0.001), LDL-C (129.6 ± 29.3 vs. 109.8 ± 28.9, p < 0.001) and HDL-C (37.7 ± 9.7 vs. 36 ± 9.3, p = 0.046) compared to the patients with 3-month LDL-C decrease < 40%. However, there was no difference in triglyceride levels between the 2 groups (121.6 ± 129.2 vs. 121.2 ± 87.6, p = 0.97).
Medication at emergent department and discharge (Table 3)
Table 3. Medications of two study groups.
| 3 months LDL-C decrease ≥ 40% | 3 months LDL-C decrease < 40% | ||
| (Group 1) N = 165 | (Group 2) N = 397 | p value | |
| Medication at emergency department | |||
| Aspirin | 162 (100.0%) | 382 (98.7%) | 0.33 |
| Beta-blocker | 89 (75.4%) | 195 (68.9%) | 0.11 |
| Clopidogrel | 160 (97.0%) | 378 (95.2%) | 0.49 |
| Glycoprotein IIb/IIIa inhibitor | 19 (11.5%) | 42 (10.6%) | 0.77 |
| Heparin | 161 (99.4%) | 378 (98.2%) | 0.45 |
| Medications at discharge | |||
| Aspirin | 152 (93.8%) | 348 (89.2%) | 0.11 |
| Beta-blocker | 107 (64.8%) | 226 (57.9%) | 0.09 |
| Clopidogerl | 160 (98.2%) | 369 (98.1%) | 1 |
| ACEI or ARB | 154 (93.3%) | 364 (91.7%) | 0.51 |
| Statin use at discharge | |||
| No statin | 13 (7.8%) | 195 (49.1%) | < 0.001 |
| Rosuvastatin | 115 (69.7%) | 134 (33.8%) | < 0.001 |
| Atorvastatin | 29 (17.6%) | 57 (14.4%) | 0.37 |
| Simvastatin + Ezitimide | 6 (3.6%) | 6 (1.5%) | 0.12 |
| Other statins | 2 (1.2%) | 5 (1.3%) | 1 |
ACEI, angiotensin converting enzyme inhibitors; ARB, angiotensin receptor blocker; LDL-C, low density lipoprotein-cholesterol.
Regarding medications administered at the emergency department, there was no significant difference in the percentage of aspirin, beta-blocker, clopidogrel, glycoprotein IIb/IIIa inhibitor and heparin use between group 1 and group 2 AMI patients.
The patients with 3-month LDL-C decrease ≥ 40% had a similar percentage of drug use at the time of discharge with those patients with 3-month LDL-C decrease < 40%, including: aspirin, beta-blocker, clopidogrel and ACEI or ARB use.
Regarding statin use at the time of discharge, the patients with 3-month LDL-C decrease ≥ 40% had a higher percentage use of statin than those patients with 3-month LDL-C decrease < 40% (91.5% vs. 50.9%, p < 0.001), especially use of rosuvastatin (69.7% vs. 33.8%, p < 0.001). There was no difference in use of atorvastatin, simvastatin with ezitimide and other statins between these 2 groups.
Follow-up laboratory data (Figure 1)
Figure 1.
Fiver year follow-up low density lipoprotein-cholesterol (LDL-C) data between two groups. The patients with 3-month LDL-C decrease ≥ 40% had higher baseline LDL-C and lower 3-month, 1-year, 2-year, 3-year, 4-year and 5-year LDL-C than the patients with 3-month LDL-C decrease < 40%. * Indicates statistical significance (p < 0.05).
In Figure 1, the patients with 3-month LDL-C decrease ≥ 40% had a higher baseline LDL-C and a lower 3-month, 1-year, 2-year, 3-year, 4-year and 5-year LDL-C than the patients with 3-month LDL-C decrease < 40% (Figure 1).
Long-term outcomes (Figure 2, Figure 3 and Figure 4)
Figure 2.
Kaplan-Meier analyses for freedom from myocardial infarction in all AMI patients. Panel A showed the patients with 3-month low density lipoprotein-cholesterol (LDL-C) decrease ≥ 40% had higher rate of freedom from myocardial infarction at 5-year follow-up than the patients with 3-month LDL-C decrease < 40% (long Rank p value = 0.006). Panel B and C showed there were no significantly different rates freedom from myocardial infarction at 5-year follow-up between patients with 3-month LDL-C decrease ≥ 30% and < 30% (long Rank p value = 0.109) or between patients with 3-month LDL-C decrease ≥ 20% and < 20% (long Rank p value = 0.321).
Figure 3.
Kaplan-Meier analyses for cardiovascular mortality in all AMI patients. Panel A showed the patients with 3-month low density lipoprotein-cholesterol (LDL-C) decrease ≥ 40% had higher 5-year survival rate than the patients with 3-month LDL-C decrease < 40% (log rank p value = 0.016). Panel B showed the patients with 3-month LDL-C decrease ≥ 30% had higher 5-year survival rate than the patients with 3-month LDL-C decrease < 30% (long Rank p value = 0.027). Panel C revealed there were no significantly different 5-year survival rates between patients with 3-month LDL-C decrease ≥ 20% and < 20% (log Rank p value = 0.245).
Figure 4.
Kaplan-Meier analyses for cardiovascular mortality in patients received statin therapy. The figure showed the patients with 3-month low density lipoprotein-cholesterol (LDL-C) decrease ≥ 40% had higher 5-year survival rate than the patients with 3-month LDL-C decrease < 40% (log rank p value = 0.01).
In Kaplan-Meier analyses for freedom from myocardial infarction (Figure 2), the patients with 3-month LDL-C decrease ≥ 40% had a higher rate of freedom from myocardial infarction at 5-year follow-up than the patients with 3-month LDL-C decrease < 40% (log rank p value = 0.006). However, there were no significantly different rates of freedom from myocardial infarction at 5-year follow-up between patients with 3-month LDL-C decrease ≥ 30% and < 30% (log rank p value = 0.11) or between patients with 3-month LDL-C decrease ≥ 20% and < 20% (log rank p value = 0.32) (Figure 2).
In Kaplan-Meier analyses for cardiovascular mortality (Figure 3), the patients with 3-month LDL-C decrease ≥ 40% had a higher 5-year survival rate than the patients with 3-month LDL-C decrease < 40% (log rank p value = 0.02). Besides, the patients with 3-month LDL-C decrease ≥ 30% had a higher 5-year survival rate than the patients with 3-month LDL-C decrease < 30% (log rank p value = 0.03). However, there were no significantly different 5-year survival rates between patients with 3-month LDL-C decrease ≥ 20% and < 20% (log rank p value = 0.25) (Figure 3).
In further subgroup analysis of patients received statin therapy, Kaplan-Meier analyses showed the patients with 3-month low density lipoprotein-cholesterol (LDL-C) decrease ≥ 40% had higher 5-year survival rate than the patients with 3-month LDL-C decrease < 40% (log rank p value = 0.01) (Figure 4).
Table 4 showed that several LDL-C parameters had an insignificant risk of cardiovascular death, including baseline LDL-Cl > 100 mg/dl, 3rd month LDL-C > 70 mg/dl, 3rd month LDL-C > 100 mg/dl, 3rd month LDL-C decreased < 20%, and 3-month LDL-C decreased < 30%. Only 3-month LDL-C < 40% parameter was significantly related to cardiovascular death (HR: 9.62, 95% CI 1.18-78.62, p < 0.04).
Table 4. Hazard ratio for cardiovascular mortality.
| Variable | Hazard ratio | p value |
| Baseline low density lipoprotein-cholesterol > 100 mg/dl | 0.76 (0.27-2.15) | 0.6 |
| 3-month low density lipoprotein-cholesterol > 100 mg/dl | 1.24 (0.52-2.18) | 0.52 |
| 3-month low density lipoprotein-cholesterol > 70 mg/dl | 1.38 (0.55-4.74) | 0.22 |
| 3-month low density lipoprotein-cholesterol decrease < 20%### | 0.49 (0.14-1.70) | 0.58 |
| 3-month low density lipoprotein-cholesterol decrease < 30%### | 1.54 (0.50-7.09) | 0.18 |
| 3-month low density lipoprotein-cholesterol decrease < 40% | 9.62 (1.18-78.62) | 0.04 |
DISCUSSION
The strengths of this study include the 5-year long-term follow-up and the detailed information on clinical risk factors. To the best of our knowledge, this is the first analysis of the role of 3-month LDL-C decrease ≥ 40% to assess long-term outcomes in patients after AMI. This 5-year follow-up study demonstrated that AMI patients with 3-month LDL-C decrease ≥ 40% had lower 3-month, 1-year, 2-year, 3-year, 4-year and 5-year LDL-C values than the patients with 3-month LDL-C decrease < 40%. Only 3-month LDL-C decrease < 40% was found to be significantly related to cardiovascular death. Furthermore, those AMI patients with 3-month LDL-C decrease ≥ 40% had a higher rate of freedom from myocardial infarction and lower cardiovascular mortality, even though these patients had higher baseline LDL-C values.
Statins were shown to play a critical role in secondary prevention of cardiovascular events.19,24-26 However, how long the LDL-C should be followed and how soon the LDL-C level should be reduced in daily practice of secondary prevention remains unknown. A previous study showed the 3-month percentage of LDL-C reduction after coronary revascularization had a substantial impact in preventing or delaying cardiovascular event recurrence.23 Even though LDL-C exceeded the guideline-recommended goal, cardiovascular event recurrence can be delayed with sufficient reduction of LDL-C during the early period after coronary revascularization.23 However, no previous publication mentioned the association between 3-month improvement of LDL after AMI and long-term outcome. The results of the present study suggest that LDL-C decrease < 40% at 3-months could be a useful predictor for cardiovascular death.
Statin use has been proven to reduce the risk of recurrent cardiovascular events and improve survival in patients with AMI.15-21 However, in this study, 49.1% of patients in the group of LDL-C reduction less than 40% were not given statins at discharge. However, only 7.8% of patients with 3-month LDL-C decrease ≥ 40% did not receive statins. The beneficial effect, as shown above, may be related to the pleiotropic effects of statin or achieved lower LDL-C level in ≥ 40% group. Therefore, subgroup analysis of patients received statin therapy was done. After exclusion of the patient without statin use at discharge, Kaplan-Meier analyses still showed that patients with 3-month low density lipoprotein-cholesterol (LDL-C) decrease ≥ 40% had higher 5-year survival rate than patients with 3-month LDL-C decrease < 40% (log rank p value = 0.01) (Figure 4). This result further supported lower LDL-C level ≥ 40% play an important role in long-term outcomes in patients after AMI.
In this study, only the 3-month LDL-C < 40% parameter was shown to be significantly related to cardiovascular death (HR: 9.62, 95% CI 1.18-78.62, p < 0.04), but not other LDL-C parameters, including baseline LDL-C > 100 mg/dl, 3rd month LDL-C > 70 mg/dl, 3rd month LDL-C > 100 mg/dl, 3rd month LDL-C decrease < 20% and 3-month LDL-C decrease < 30%. These results also confirmed that patients with 3-month LDL-C decrease ≥ 40% had better 5-year outcomes than the patients with 3-month LDL-C decrease < 40%, even though a higher baseline LDL-C was present in these groups (Figure 1). A recent ESC guideline proposed LDL-C < 70 mg or a reduction > 50% in high-risk patients.27 However, this topic has not been examined in an Asian population. The CREDO-Kyoto Registry Cohort-2 trial showed, in patients post first coronary revascularization, the risk for MACE was significantly higher in the LDL-C ≥ 120 mg/dl group.28 Whereas, there were insignificant differences of MACE in the LDL-C = 100-119 mg/dl group and the LDL-C < 80 mg/dl group.28 Sakamoto and Ogawa also mentioned about “Just make it lower” is an alternative strategy of lipid-lowering therapy with statins in Asian patients.29 Furthermore, the beneficial effects of statin therapy were shown to vanish when LDL-C is below a certain level in AMI patients.30 These previous researches28-30 supported our findings in this study.
Study limitations
There were several limitations to our study. First, our sample size was relatively small. Furthermore, this was a single center study. It might be necessary to further confirm the results of this study by another large cohort multi-center study. Whereas, this study was an observational study and the differences among groups might influence the results. However, most of the baseline characteristics, complication rates, baseline laboratory data and medications between these two study groups were shown to be insignificant different (Table 1, Table 2 and Table 3). Furthermore, the adherence of statin and effect of different statins were not investigated in this study.
CONCLUSIONS
After AMI, 3-month LDL-C decrease < 40% was identified to be a significant risk factor to assess 5-year cardiovascular death. The patients with 3-month LDL-C decrease ≥ 40% had a higher rate of freedom from myocardial infarction and lower cardiovascular mortality, even though these patients had higher baseline LDL-C value.
REFERENCES
- 1.Wong CP, Loh SY, Loh KK, et al. Acute myocardial infarction: clinical features and outcomes in young adults in Singapore. World J Cardiol. 2012;4:206–210. doi: 10.4330/wjc.v4.i6.206. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Shyu KG, Wu CJ, Mar GY, et al. Clinical characteristics, management and in-hospital outcomes of patients with acute coronary syndrome - observations from the Taiwan ACS full spectrum registry. Acta Cardiol Sin. 2011;27:135–144. [Google Scholar]
- 3.Li YH, Yeh HI, Tsai CT, et al. 2012 guidelines of the Taiwan Society of Cardiology (TSOC) for the management of ST-segment elevation myocardial infarction. Acta Cardiol Sin. 2012;28:63–89. [Google Scholar]
- 4.Huang WC, Chiou KR, Liu CP, et al. Multidetector row computed tomography can identify and characterize the occlusive culprit lesions in patients early (within 24 hours) after acute myocardial infarction. Am Heart J. 2007;154:914–922. doi: 10.1016/j.ahj.2007.07.002. [DOI] [PubMed] [Google Scholar]
- 5.Liu CP, Lin YH, Lin MS, et al. Evaluation of myocardial infarction patients after coronary revasculation by dual-phase multi-detector computed tomography:now and in future. World J Cardiol. 2013;5:115–118. doi: 10.4330/wjc.v5.i4.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Hsu HP, Jou YL, Lin SJ, et al. Comparison of in-hospital outcome of acute ST elevation myocardial infarction in patients with versus without diabetes mellitus. Acta Cardiol Sin. 2011:145–151. [Google Scholar]
- 7.Hsu HP, Jou YL, Wu TC, et al. Hyperglycemia increases new-onset atrial fibrillation in patients with acute ST-elevation myocardial infarction. Acta Cardiol Sin. 2012;28:279–285. [Google Scholar]
- 8.Huang SS, Leu HB, Lu TM, et al. The impacts of in-hospital invasive strategy on long-term outcome in elderly patients with non-ST-elevation myocardial infarction. Acta Cardiol Sin. 2013;29:115–123. [PMC free article] [PubMed] [Google Scholar]
- 9.Wang WH, Hsiao SH, Chiou KR, et al. Limited efficacy of myocardial tissue doppler for predicting left ventricular filling pressure, severe pulmonary edema, and respiratory failure in acute myocardial infarction. Acta Cardiol Sin. 2012;28:206–215. [Google Scholar]
- 10.Huang WC, Liu CP, Wu MT, et al. Comparing culprit lesions in ST-segment elevation and non-ST-segment elevation acute coronary syndrome with 64-slice multidetector computed tomography. Eur J Radiol. 2010;73:74–81. doi: 10.1016/j.ejrad.2008.09.024. [DOI] [PubMed] [Google Scholar]
- 11.Huang WC, Wu MT, Chiou KR, et al. Assessing culprit lesions and active complex lesions in patients with early acute myocardial infarction by multidetector computed tomography. Circ J. 2008;72:1806–1813. doi: 10.1253/circj.cj-08-0165. [DOI] [PubMed] [Google Scholar]
- 12.Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362:801–809. doi: 10.1038/362801a0. [DOI] [PubMed] [Google Scholar]
- 13.Ross R. Atherosclerosis--an inflammatory disease. New Engl J Med. 1999;340:115–126. doi: 10.1056/NEJM199901143400207. [DOI] [PubMed] [Google Scholar]
- 14.Ross R, Harker L. Hyperlipidemia and atherosclerosis. Science. 1976;193:1094–1100. doi: 10.1126/science.822515. [DOI] [PubMed] [Google Scholar]
- 15.Patti G, Pasceri V, Colonna G, et al. Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial. J Am Coll Cardiol. 2007;49:1272–1278. doi: 10.1016/j.jacc.2007.02.025. [DOI] [PubMed] [Google Scholar]
- 16.Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. New Engl J Med. 2004;350:1495–1504. doi: 10.1056/NEJMoa040583. [DOI] [PubMed] [Google Scholar]
- 17.Stenestrand U, Wallentin L Swedish Register of Cardiac Intensive C. Early statin treatment following acute myocardial infarction and 1-year survival. JAMA. 2001;285:430–436. doi: 10.1001/jama.285.4.430. [DOI] [PubMed] [Google Scholar]
- 18.Fonarow GC, Wright RS, Spencer FA, et al. Effect of statin use within the first 24 hours of admission for acute myocardial infarction on early morbidity and mortality. Am J Cardiol. 2005;96:611–616. doi: 10.1016/j.amjcard.2005.04.029. [DOI] [PubMed] [Google Scholar]
- 19.Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study:a randomized controlled trial. JAMA. 2001;285:1711–1718. doi: 10.1001/jama.285.13.1711. [DOI] [PubMed] [Google Scholar]
- 20.Aronow HD, Topol EJ, Roe MT, et al. Effect of lipid-lowering therapy on early mortality after acute coronary syndromes: an observational study. Lancet. 2001;357:1063–1068. doi: 10.1016/S0140-6736(00)04257-4. [DOI] [PubMed] [Google Scholar]
- 21.Llevadot J, Giugliano RP, Antman EM, et al. Availability of on-site catheterization and clinical outcomes in patients receiving fibrinolysis for ST-elevation myocardial infarction. Eur Heart J. 2001;22:2104–2115. doi: 10.1053/euhj.2001.2622. [DOI] [PubMed] [Google Scholar]
- 22.Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110:227–239. doi: 10.1161/01.CIR.0000133317.49796.0E. [DOI] [PubMed] [Google Scholar]
- 23.Nishiwaki T, Kishi D, Yoshie F, et al. Relationship between LDL-C reduction after coronary revascularization and prevention of recurrence of cardiovascular events. J Pharm Pharm Sci. 2010;13:254–262. doi: 10.18433/j3hg6q. [DOI] [PubMed] [Google Scholar]
- 24.O’Keefe JH, Jr., Cordain L, Harris WH, et al. Optimal low-density lipoprotein is 50 to 70 mg/dl: lower is better and physiologically normal. J Am Coll Cardiol. 2004;43:2142–2146. doi: 10.1016/j.jacc.2004.03.046. [DOI] [PubMed] [Google Scholar]
- 25.Thompson PL. Clinical relevance of statins: instituting treatment early in acute coronary syndrome patients. Atheroscler Suppl. 2001;2:15–19. doi: 10.1016/s1567-5688(00)00005-2. [DOI] [PubMed] [Google Scholar]
- 26.Thompson PL, Meredith I, Amerena J, et al. Effect of pravastatin compared with placebo initiated within 24 hours of onset of acute myocardial infarction or unstable angina: the Pravastatin in Acute Coronary Treatment (PACT) trial. Am Heart J. 2004;148:e2. doi: 10.1016/j.ahj.2003.10.052. [DOI] [PubMed] [Google Scholar]
- 27.European Association for Cardiovascular P, Rehabilitation, Reiner Z. et al. ESC/EAS Guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) Eur Heart J. 2011;32:1769–1818. doi: 10.1093/eurheartj/ehr158. [DOI] [PubMed] [Google Scholar]
- 28.Natsuaki M, Furukawa Y, Morimoto T, et al. Intensity of statin therapy, achieved low-density lipoprotein cholesterol levels and cardiovascular outcomes in Japanese patients after coronary revascularization. Perspectives from the CREDO-Kyoto regis. 2012;76:1369–1379. doi: 10.1253/circj.cj-11-1356. [DOI] [PubMed] [Google Scholar]
- 29.Sakamoto T, Ogawa H. “Just make it lower” is an alternative strategy of lipid-lowering therapy with statins in Japanese patients: LDL-cholesterol: the lower, the better; is it true for Asians? (Con) Circ J. 2010;74:1731–1741. doi: 10.1253/circj.cj-10-0537. [DOI] [PubMed] [Google Scholar]
- 30.Lee JH, Park SH, Yang DH, et al. Threshold level of low-density lipoprotein cholesterol for the short-term benefit of statin therapy in the acute phase of myocardial infarction. Clin Cardiol. 2012;35:211–218. doi: 10.1002/clc.20984. [DOI] [PMC free article] [PubMed] [Google Scholar]