Cardiovascular Lipid Risk Factors and Rate of Cardiovascular Events After Myocardial Revascularization

Mailing Address: Cosor Oana Catalina Str.Arh.V.Vlad,bl 13 ,sc D,ap 2 – 13. Postal Code 035332, Timisoara Romania E-mail: andrei.csr@gmail.com Cardiovascular Lipid Risk Factors and Rate of Cardiovascular Events After Myocardial Revascularization Cosor Oana Catalina,1 Bucur Adina,1 Baibata Emilia Dana Smarandita,1 Dragomir Angela,2 Gaita Dan,1 Mancas Silvia1 University of Medicine and Pharmacy Victor Babes Timisoara1; The Institute of Cardiovascular Disease Timisoara2 Romania


Introduction
Coronary heart disease remains "the scourge of the modern world" despite advances made in the field.It is a public health problem, and the leading cause of premature death in Europe and worldwide. 1 this study, we focused on understanding the evolution of the atherothrombotic process in coronary symptomatic patients who underwent coronary revascularization: percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).
The relationship between low-density lipoprotein cholesterol (LDL-c) and the incidence of cardiovascular events has been demonstrated by numerous epidemiological studies: CARDS 2 ASPEN 3 ASCOT. 4The New European Society of Cardiology (ESC) Guidelines for Cardiovascular Disease Prevention recommended LDL-c target levels of lower than 70 mg/dL for coronary patients at high risk and very high risk 5 .] ELIGIBILITY n = 341 (PTCA, CABG)

Original Article
The hypothesis of our research was that an inefficient control of cardiovascular risk factors would have a long-term effect on the incidence of fatal and non-fatal cardiovascular events.In this context, our study aimed to analyze the incidence of fatal and non-fatal cardiovascular events in coronary patients under statin therapy years after coronary revascularization, following the ESC prevention of cardiovascular disease program criteria. 5

Methods
This is a single-center study conducted at the Institute of Cardiovascular Disease, Timisoara, Romania.The inclusion criteria followed the EUROASPIRE IV protocol.A total of 375 consecutive coronary patients aged 18-80 years with definite diagnosis of revascularization for coronary artery disease (PCI, CABG) were retrospectively identified.Of them, 341 were considered eligible and 341 were included in the study (Figure 1).Clinical data of patients were assessed at three time points -at T0, when successful revascularization was identified, at T1 (from 6 months to 3 years post-myocardial revascularization), and at T2 (from 3 to 5 years post-myocardial revascularization).
The following data was collected on an electronic database: lipid profile data -total cholesterol (TC); triglycerides, (TG); high-density lipoprotein cholesterol (HDL-c); LDL-c; non-HDL-c calculated as TC minus HDL-c 8 -number of fatal / non-fatal cardiovascular events; major adverse cardiovascular events (MACE): cardiovascular death, noncardiovascular death, restenosis, stroke / transient ischemic attack (TIA)electrostimulation by pacemaker, hospitalization for reintervention -percutaneous transluminal coronary angioplasty (PTCA) or CABG, hospitalization for heart failure, diagnosis of diabetes mellitus.New lipid risk was evaluated at T0 and T1, following the European Cardiovascular Prevention criteria (5).The rate of fatal and nonfatal cardiovascular events was analyzed based on the potential cardiolipidic risk.
Patients' follow-up was conducted by a questionnaire validated for the countries that participated in the EUROASPIRE IV study. 6At inclusion, we used the post-revascularization protocols specified in the ESC guidelines for secondary cardiovascular prevention (2012) 9 , adopted by the Romanian Society of Cardiology.

Statistical analysis
Statistical analysis was performed with SPSS 17.0 statistics, including 31 statistical variables (numerical and categorical).Time variable was calculated from the date the patient underwent coronary revascularization until January 2015, when MACE events were detected as present or absent.Normality of the variables was tested by the Shapiro-Wilk test.Differences between variables with only two categories were assessed by the non-parametric Mann-Whitney test.A p-value < 0.05 was set as statistically significant.

Results
Of 375 consecutive coronary patients, 341 patients (64.22 ± 8.90 years, 81.52% male) were included in our study.Baseline characteristics of patients are presented in Table 1.At T0, 52.5% of patients had undergone CABG, 43.1% PCI, and 4.4% had undergone both procedures.
At inclusion in the study, there was a high prevalence of modifiable cardiovascular risk factors (Table 1.1).

Statin therapy for LDL-c control remains a pertinent therapeutic target (Table 2)
At T1, 76.2% of participants had LDL-c values ≥ 80 mg/dL.In fact, only 5% of revascularized patients receiving statins that reached the target LDL-c value recommended by the ESC guidelines. 5,10,11n-HDLc or secondary lipid target and residual risk: using a non-HDL-c target < 110 mg/dL, we found that 30.8% of patients at T0 and 34.9% at T1 achieved these levels (p = NS) dL.There was no statistically significant differences between mean non-HDL-c atT0 (135.2 ± 44.95 mg/dL) and T1 (129.13 ± 40.9 mg/dL).

MACE rates and post-revascularization cardiovascular risk:
the MACE rate at T2 was 7.9% in a median follow-up time of 4.33 years.
There was a positive and statistically significant association between primary lipid target of LDL-c at T1 and MACE (p = 0.039, chi test, 95% CI) (Table 3).In addition, there was a significant difference in mean non-HDL-c between the MACE categories at T1 (p = 0.02, Kruskal Wallis test, 95% CI) (Figure 2).
The incidence of heart failure, defined by the value of ejection fraction was significantly higher in patients with increased non-HDL-c, not responsive to medications at T1 (p = 0.007, Mann-Whitney test, 95% CI).
Newly diagnosed cases of diabetes were significantly more frequent in patients with increased non-HDL-c at T1 (p = 0.017, Mann-Whitney test, 95% CI).
There was no significant difference between the incidence of MACE and the type of revascularization procedures.

Discussion
Our study demonstrates a high cardiovascular risk among coronary patients after 4.33 years of myocardial revascularization.

Original Article
The drugs prescribed to be used in association with statins were platelet aggregators, beta-blockers, angiotensin converting enzyme inhibitors and angiotensin receptor blockers, in accordance with the ESC guidelines for secondary cardiovascular prevention.
Analysis of the relationship between the medications and achievement of target values of modifiable risk factors was previously published by our group. 9eduction in systolic blood pressure under medication was achieved in 39.58% of subjects enrolled in this study; cardiometabolic risk was reduced under the maximum dose of statin.Although the primary lipid target was reached in only 5% of patients, better outcomes were found in the secondary lipid target, non-HDL-c.
The high metabolic risk in these coronary patients is supported by dyslipidemia and high incidence of diabetes at T1, which justifies the implementation of energetic approaches toward lifestyle changes associated with the use of proper medication in revascularized patients.
Our study did not set out to analyze the compliance of patients to post-revascularization recovery programs, which would have contributed to interpretation of our results.A low compliance to these programs and cardiovascular preventive approaches may be related to the development of atherothrombosis in coronary patients, and might explain the prevalence of cardiovascular events (7.9%) at T2 and a median survival time of 4.33 years in our study group.Further studies to evaluate the compliance of patients to these approaches would be helpful.
Our study corroborates the need for strategies to control modifiable cardiovascular risk factors. 9,12,13espite the use of medications, patients undergoing myocardial revascularization remain at risk of cardiovascular events related to atherosclerosis progression and other metabolic diseases. 9,11sults from the EUROASPIRE IV 6 pointed out that the Joint European Societies Guidelines on Cardiovascular Prevention recommendations are achieved in a still low proportion of coronary patients across Europe.In our study, only a modest percentage of revascularized coronary patients met the ESC Guidelines recommendations for LDLc -targets. 10,11Although statin was prescribed to nearly 95% of patients at T1, the LDL-c levels were not reached by most of them.
Reiner et al. 13 emphasized the need to reduce LDL-c levels after a cardiovascular event to reduce coronary heart disease mortality and morbidity. 13Other authors suggested several reasons for the mediocre response during statin therapy: inadequate dose, non-adherence to prescribed dose, statin resistance and / or intolerance, and side effects. 14,15However, our results confirm the association between increased LDL-c levels with cardiovascular event rates.
We wonder if we can predict residual lipid risk in revascularized, coronary patients in use of statins.In our study group, there were significant differences in mean HDL-c and MACE rates at T2 as compared with other time points.Furthermore, they were correlated with the rate of restenosis, prevalence of heart failure and incidence of diabetes.][16] It seems that non-HDL would be a better predictor than LDLc of unstable atherosclerotic plaque. 17iner et al. reported that 12.2% of coronary patients in whom the LDLc target value was reached had pathological levels of non-HDL-c.In our sample, only 7.33% patients had non-HDL-c levels > 110 mg/dL and LDL-c < 80 mg/dL after myocardial revascularization.
[20] Our study has some limitations.First, baseline characteristics of participants were defined in a relatively late stage of coronary artery disease, i.e. at the time of myocardial revascularization.In addition, our sample was somewhat biased, since it was composed exclusively of patients treated at Timisoara Institute of Cardiovascular Diseases, which is a specialized treatment center, and therefore, the results cannot be to all patients with coronary revascularization.[18][19][20][21]

Conclusions
The study highlights the need to control lipid risk factors after myocardial revascularization procedures, even at long-term, to minimize the risk of cardiovascular events in patients with coronary diseases.

Figure 2 -
Figure 2 -Mean LDL-c levels at T1 and major adverse cardiovascular events (MACE) rate at T2

Table 2 -
Lipid target levels and number of patients in whom these levels were reached at T1

Table 3 -
Relationship between LDL-c and major adverse cardiovascular events (MACE) at T1