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ORIGINAL ARTICLE
Year : 2021  |  Volume : 11  |  Issue : 4  |  Page : 186-192

Impact of low early high-density lipoprotein cholesterol on inhospital outcome and short-term prognosis in patients with acute coronary syndrome


Department of Cardiology, Tanta University, Tanta, Egypt

Date of Submission18-Nov-2020
Date of Decision01-Dec-2020
Date of Acceptance14-Dec-2020
Date of Web Publication25-Oct-2021

Correspondence Address:
Dr. Tarek E Elkholy
62 Elmotamyz District, 6th of October City, Giza
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jicc.jicc_79_20

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  Abstract 


Background: Acute coronary syndrome (ACS) is a cardiac emergency and constitutes a major burden globally. Association between serum lipid and ACS is established many years ago. Our study tried to have more information about the impact of high-density lipoprotein cholesterol (HDL-C) on inhospital outcome and short-term prognosis of patients with ACS. Materials and Methods: The study was a prospective comparative study. Clinical and chemical and interventional evaluation was done in hospital settings. A total number of 50 patients were included in the study and divided into two groups. Patients with low HDL-C level were in Group I and patients with normal HDL-C were in Group II. Results: Group I populations had more inhospital complications than Group II represented in acute heart failure (48% vs. 13%), cardiogenic shock (40% vs. 6%), complex coronary lesions (57% vs. 20%), and prolonged hospital stay (54% vs. 20%). A statistical significance was found regarding these variables (P < 0.05). Regarding the outcome after 1 month, it is observed that patients of Group I significantly experienced heart failure (59.38% vs. 21.43%) and worsening angina (62.5% vs. 28.57%) with a statistically significant difference. In contrast, there is no statistically significant difference regarding myocardial infarction, new cerebrovascular events, shock, and mortality. Conclusion: The study showed a strong association of HDL-C level with inhospital adverse events of ACS patients in addition to short-term adverse events. Complications of ACS were more in patients with low HDL-C level.

Keywords: Acute coronary syndrome, high-density lipoprotein cholesterol, ischemic heart disease


How to cite this article:
Elkholy TE, Saeed ES, Abo Omar MA, El-barbary YH. Impact of low early high-density lipoprotein cholesterol on inhospital outcome and short-term prognosis in patients with acute coronary syndrome. J Indian coll cardiol 2021;11:186-92

How to cite this URL:
Elkholy TE, Saeed ES, Abo Omar MA, El-barbary YH. Impact of low early high-density lipoprotein cholesterol on inhospital outcome and short-term prognosis in patients with acute coronary syndrome. J Indian coll cardiol [serial online] 2021 [cited 2021 Dec 5];11:186-92. Available from: https://www.joicc.org/text.asp?2021/11/4/186/329153




  Introduction Top


Being able to have the prediction of the inhospital complications of patients with acute coronary syndrome (ACS) at the time of admission is of a great significance when trying to determine treatments. Consequently, many large studies tried to evaluate possible predictors of inhospital complications in ACS patients as well as short-term complications that may happen.

ACS includes many risk factors, such as aging, male gender, smoking, hypertension, diabetes mellitus, renal failure, obesity, hyperlipidemia, history of premature coronary artery disease (CAD), and sedentary lifestyle.[1]

There is a solid clinical evidence showing that low high-density lipoprotein (HDL) is a pertinent risk factor for CAD due to reverse cholesterol transportation, anti-inflammatory, and antioxidant properties of HDL-C.[2],[3]

A low level of HDL has been interrelated to be an important predictor for cardiovascular adverse effects.[4] However, many people who survived of ACS have been involved in prospective studies to examine the use of statins for the secondary prevention of myocardial infarction; randomized-control trials have not recorded the initial lipid profile data of ACS at admission and during hospital stay of those patients.

Thus, the relation between the inhospital outcome and the HDL levels of samples drawn early after arrival remains undefined and poorly studied.

Furthermore, there is little information regarding the predictive value of the HDL cholesterol (HDL-C) levels for detecting cardiovascular events and their effect on early clinical outcomes after a hospital stay.

Aim of the work

Our aim is to evaluate the association between the low early HDL-C levels and inhospital adverse outcomes in addition to investigating the impact of HDL-C level on the early prognosis of ACS patients after receiving medical treatment or invasive treatment after 1 month from the hospital stay.


  Materials and Methods Top


This prospective study was conducted in the Cardiology Department, Tanta University Hospital, within 6 months in the period from September 2019 to March 2020 and included 50 consecutive patients admitted to the emergency department or cardiac care unit with the diagnostic criteria for ACS with the aim to find the correlation between the level of HDL-C and inhospital outcome of those patients.

Classification of high-density lipoprotein

Patients were evaluated by HDL levels defined as low HDL levels (10–39 mg/dL), normal HDL level (40–59 mg/dL), and high HDL level (60–100 mg/dL). This grouping was chosen based on the classification of HDL levels by the Adult Treatment Panel III from the NCEP.[5]

Then, patients were classified into two groups: Group I with HDL level in male ≥40 mg/dl and in female <50 mg/dl and Group II with HDL level in male ≥40 mg/dl and in female ≥50 mg/dl

Subjects included

Patients presented with ischemic symptoms (typical anginal chest pain, atypical chest discomfort, and/or acute onset breathlessness) lasting for 10 min at least within the last 24 h combined with either ST-segment changes (persistent ST-segment elevation in two successive leads or ST-segment depression of at least 0.5 mm or transient ST-segment elevation of 0.5–1.0 mm) and/or positive cardiac biomarkers (either elevated creatine kinase-MB (ck-mb or troponin levels).

Subjects excluded

Patients having a past history of percutaneous coronary intervention (PCI), coronary artery bypass graft, dilated cardiomyopathy, congenital heart diseases, and valvular affection; patients with serious comorbidities; and patients who refused to sign consent or with insufficient data were excluded from the study.

  • All patients will be subjected to the following during hospital stay:


    1. Thorough history taking
    2. Complete clinical examination
    3. 12-lead electrocardiogram
    4. Transthoracic echocardiography
    5. Routine laboratory investigations including lipid profile within 24 h from patient's admission
    6. All patients will be treated either with PCI or medical treatment
    7. Inhospital adverse events of all the patients were evaluated (heart failure, arrhythmias, heart block, complexity of coronary artery lesions [left main lesion and/or three-vessel disease], cardiogenic shock, duration of hospitalization, cardiac arrest, and death).


  • All patients will be re-evaluated after 1 month of being discharged from the hospital and adverse outcomes will be evaluated as heart failure, myocardial infarction, worsening angina, new cerebrovascular events, cardiogenic shock, and death.


Statistical analysis

Analysis of data was done using the Statistical Package for the Social Sciences (SPSS) version 20 (Chicago, Illinois, USA).[6] Qualitative data were described using number and percent. Quantitative data were described using range (minimum and maximum), mean, standard deviation, and median.

The tests include Chi-square test for categorical variables to compare between different groups, Fisher's Exact test for correction for Chi-square when >20% of the cells expected count <5, Student's t-test was used for normally distributed quantitative variables to compare between two studied groups, and Mann–Whitney test for abnormally distributed quantitative variables to compare between two studied groups.

Correlations between the different variables were done using Pearson correlation coefficient for the parametric data and Spearman correlation coefficient for the nonparametric data. P ≤ 0.05 was used as a cutoff value for the significance of results. Reliability analysis was performed by calculating the intraclass correlation coefficient between graders to assess inter-grader variation.


  Results Top


Regarding symptoms, chest pain, either typical, atypical, or breathlessness, between the two groups was not significant with P values (0.797, 0.773, and 0.248), respectively. Similarly, a pattern of infarction between the two groups has no statistically significant difference as depicted in [Table 1].
Table 1: Clinical presentation of the study subjects

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There was no statistically significant difference between the two groups in respect to the age, sex, risk factors, and diagnosis as shown in [Table 2] and [Table 3].
Table 2: Distribution of patients by clinical diagnosis

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Table 3: Distribution of the study subjects according to the risk factors

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With respect to hemodynamic status, there was no much difference in mean pulse and blood pressure in the two groups with no statistical significance, whereas it is noted that ejection fraction was greatly lower in Group I than Group II with (P = 0.025) as mentioned in [Table 4]
Table 4: Distribution of patients according to the hemodynamics

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Mean serum cholesterol and triglyceride levels were not significantly different between the two groups (P = 0.078 and P = 0.459, respectively). On the contrary, the mean low-density lipoprotein (LDL) was significantly low in Group I than in Group II (P = 0.026). In addition, the mean HDL-C was significantly less in Group I than Group II (P < 0.001) which was shown in [Table 5].
Table 5: Distribution of patients according to the serum lipid values

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Regarding in-hospital adverse events, patients of group I developed acute decompensated heart failure (48.57% vs 13.33%, p= 0.019), severe coronary disease (57.14% vs 20% ,p=0.016) and cardiogenic shock (40% vs 16.67%, p= 0.018) more than group II with statistical significance. There is no statistical difference in arrhythmia (p= 0.0849), heart block, cardiac arrest (p= 0.607) and death (p=0.820) between two groups. In addition, group I patients had prolonged stay at hospital in contrast to group II patients (p<0.025) as provided in [Table 6].
Table 6: Comparison of outcome during hospitalization between the two groups

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When we display the outcome after 1 month of discharge, it is noted that patients of Group I significantly experienced heart failure (59.38% vs 21.43%, P = 0.018) and worsening angina (62.5% vs. 28.57%, P = 0.034). In contrast, there is no statistically significant difference regarding myocardial infarction, new cerebrovascular events, shock, and mortality as described in [Table 7].
Table 7: Comparison of individual postdischarge outcome between the two groups

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  Discussion Top


It is generally postulated that patients with low HDL carry high liability to develop more adverse outcomes and mortality than those with normal to high HDL during hospital stay.[7],[8] However, evidences for this postulation are lacking. The only evidence of plasma lipids as prognostic factors is provided by Olsson et al., who evaluated the cohort of the MIRACL trial and demonstrated HDL-C as an independent predictor of events, as opposed to LDL-cholesterol.[4] However, this result was obtained during a follow-up of 16 weeks and prediction of inhospital events was not evaluated, what makes our data original in regard to the focus of events during the acute phase of ACS.

The CRUSADE study[9] and ACTION Registry-GWTG,[10] two large studies, that studied the non-ST-segment elevated myocardial infarction assessed the HDL-C on the admission. However, both the registries revealed that patients with low HDL-C had a greater risk of inhospital death than those with normal HDL-C level; the primary data were lost in half of the patients in these studies. Moreover, similar studies analyzing the initial lipid measurements in ACS patients fail to show the interval between the arrival of patients and the time where the blood samples were taken.[4],[7]

Our study was focused to get the relation of HDL-C with inhospital adverse events and short-term prognosis of patients with ACS.

Among 50 patients with ACS, we found that 35 (70%) patients had low HDL level. Roe MT et al. (2012) said that among NSTE-ACS patients, 18.1% had very low and 34.5% had low HDL-C level, which is slightly lower than our findings.[9] Our study showed that the prevalence (70%) of low HDL-C in ACS patients was the greatest among other reported researches on ACS which were between 28% and 57%. One probable reason could be linked to the high incidence of metabolic syndrome in people of Egypt.[11] In addition, a high percentage of metabolic syndrome[2] and obesity[12] has also been studied before in this region.

Our study revealed that the total number of males was more than the female patients (72% vs. 28%). Our finding had the support of Al-Rasadi et al. (77% vs. 23%), and Faizal et al. (80.63% vs. 19.37%).[13],[14]

We found that chest discomfort was the most common complaint with its different patterns in both the groups of patients. The difference in presentation with typical chest pain and atypical chest pain between two groups was not significant (62.86% vs. 66.67%, P = 0.797) and (22.86% vs. 26.67%, P = 0.773), respectively. This was supported by Hermann et al.[15] However, typical angina complaint is more prevalent in the two groups than the atypical angina.

Our study detected that difference in the history of smoking, high blood pressure, and DM was not significant statistically. The findings of our study were supported by the observations of Khan and Mojumder (2009), Al-Rasadi et al., Manurung, and Faizal et al.[13],[14],[16]

Our study found that left ventricular function was affected in Group I patients. The mean ejection fraction of Group I was greatly lower than patients of Group II (P = 0.025); however, there was no great difference regarding pulse and blood pressure between the two groups.

Our findings revealed that more patients in Group I demonstrate a shock state than Group II during hospitalization (40% vs. 6.67%, P = 0.018). Similarly, Barter PJ et al. (2004). found that low HDL-C was linked to high incidence of cardiogenic shock, compared with the normal to high HDL-C group (P = 0.001).[2]

The rate of cardiogenic shock in low HDL-C group is poorly studied, whereas in our study, low HDL-C was an independent determinant of cardiogenic instability in ACS. This could be explained in the correlation between low early HDL-C and severe coronary lesions, catecholamines and inotropes support, and/or use of assist devices.[17] Furthermore, Zeller et al.[18] showed that high blood sugar and low HDL-C levels had a solid relation with severe heart failure and hyperglycemia was an independent determinant of cardiogenic shock, and further studies are needed to confirm this new association between low HDL and cardiogenic shock.

Similarly, patients in Group I had higher rates of acute heart failure than those in Group II (48.57% vs. 13.33%, P = 0.019). This was supported by theories of Mehra, M.R., et al and Iwaoka, M., et al. of contribution of HDL dysfunction to the occurrence and development of heart failure. First, inflammation and heart failure are both connected. Second, heart failure is associated with insulin resistance. Both inflammation and insulin resistance cause HDL dysfunction. HDL dysfunction and heart failure could reinforce each other, a pattern of cyclic causality may be found,[19],[20]

In contrast, these theories were contradicted by Faizal et al. (2009) and Al-Rasadi et al. who found no much difference between two groups of patients in regards to heart failure (23.5hi% vs 21%, p=0.029) and (CI=0.9-1.22, p=0.509) respectively.[13],[14]

It is noted from our study that patients of Group I demonstrated severe coronary disease or multivessel disease more than those of Group II with statistical significance (57.14% vs. 20%, P = 0.016). This demonstrated that low HDL level is an important and independent risk factor for the severity of CAD which was supported by Salahuddin et al.[21] and Wang et al.[22] Several angiographic findings from ACS patients have detected an inverse relationship between the incidence of multivessel coronary lesions and the HDL level.[23],[24]

Duration of hospital stay is affected by the level of HDL as demonstrated by our study as follows: patients with low HDL experienced prolonged hospital stay than those of normal or high HDL levels (54.29% vs. 20%, P = 0.025). This was supported by Al-Rasadi et al., Faizal et al., and Wolfram et al. (6.65 ± 2.04 vs. 5.09 ± 1.44 days, P < 0.001).[13],[14],[25]

In addition, length of stay was longer among patients with low HDL-C (2.7–3.1 vs. 3.2–3.8 days, P = 0.02) according to Wolfram et al.[25]

There is no statistically significant difference between the two groups in terms of arrhythmia, heart block, cardiac arrest, and death (P > 0.51). Our findings were supported by Chowdhury Muhammad Omar Faruque and Miftaul Jannath Chowdhury who revealed no difference in this regard (P > 0.05).[26] Conversely, Al-Zakwani et al. and Correia et al. stated that low HDL level contributed to a high incidence of mortality.[7],[27]

Postdischarge follow-up

Our study was focused on assessing the correlation between the initial level of HDL at time of admission and the outcome of patients within 1 month after discharge.

Among 50 patients, 7 patients of Group I died, while only one patient of Group II passed away (20% vs. 6.667%, P = 0.239) which showed no much statistical significance in mortality between the two groups. This was supported by the findings of Zhixiong Zhong, Jingyuan Hou, and Qifeng Zhan which was as follows (52% vs. 82%, P = 0528).[28] On the other side, the study of Wolfram et al. revealed that mortality up to 30 days was 0% in the high HDL group versus 3% (12 patients) in the low HDL group (P = 0.001).[25]

Our study also demonstrated more patients who sustained left ventricular failure in Group I than their peers of Group II with statistical significance (59.38% vs. 21%, P = 0.018). Masayasu Izuhara supported that by showing that patients with low HDL develop heart failure more than those with satisfactory HDL (22% vs. 15%, P < 0.001).[29]

Similarly, patients in Group I complained of frequent episodes of worsening angina more frequently than those of Group II (62.5% vs. 28.57%, P = 0.034).

In contrast, there is not much difference between the two groups regarding cardiogenic shock and cerebrovascular events.

Study limitations

Lipid blood levels may be somehow affected during the initial phase of ACS and this could have altered the estimation of HDL-C level.[30] However, a study showed little variation in lipid levels which is measured in the first few days of admission after myocardial infarction.[31] Furthermore, the sample size is small and number of patients is limited in comparison to other studies.


  Conclusion Top


The study depicts a high incidence of low HDL levels in patients with ACS and was significantly associated with a higher rate of shock, complex coronary lesions, and acute heart failure but insignificantly associated with arrhythmia, heart block, cardiac arrest, and mortality during hospital stay. Low HDL also acts as a good prognostic factor for an increased incidence of heart failure and frequent angina episodes 30 days after ACS. Although guidelines for LDL management in ACS are well known, treatment guidelines concerning HDL levels are not as clear. Therefore, the failure to know the prognostic value of low HDL-C in ACS may predispose these patients to be liable for recurrent adverse events and worse results. Studies evaluating the clinical benefit of increasing HDL-C levels in patients with ACS must be more scrutinized and developed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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