The prognostic impact of HDL-C level in patients presenting with ST-elevation myocardial infarction

Low high-density lipoprotein-cholesterol (HDL-C) concentration is among the strongest independent risk factors for cardiovascular disease, however, studies to assess the cardioprotective effect of normal or high HDL-C level are lacking.

To determine the prognostic impact of initial serum HDL-C level on in-hospital major adverse cardiovascular and cerebrovascular events (MACCE) and the one-year all-cause mortality in patients presenting with ST-elevation myocardial infarction (STEMI) we performed a retrospective analysis of the data from 1,415 patients presenting with STEMI in a tertiary-care centre equipped with a 24-hour-ready catheterisation laboratory. The period from June 2014 to June 2017 was reviewed with a follow-up as regards one-year all-cause mortality. Patients were divided into two groups according to HDL-C level. HDL-C <40 mg/dL (2.22 mmol/L) was considered low, while HDL-C ≥40 mg/dL was considered normal.

There were 1,109 patients with low HDL-C, while 306 had normal HDL-C levels, which was statistically significant (p<0.001). Total MACCE and all-cause mortality were significantly lower in patients with normal HDL-C (p=0.03 and p=0.01, respectively).

In conclusion, this retrospective study to assess the prognostic effect of HDL-C in patients presenting with STEMI, found normal HDL-C level was associated with lower in-hospital MACCE and all-cause mortality at one-year follow-up.

Introduction

Multiple risk factors have been identified for myocardial infarction (MI). Hypercholesterolaemia is one of the major risk factors for cardiovascular diseases, and has an important pathophysiological role in the development of acute ST-elevation myocardial infarction (STEMI).¹ Endothelial dysfunction, inflammation, increased thrombogenicity, and plaque vulnerability are the main underlying mechanisms explaining the complex interaction between hypercholesterolaemia and STEMI.^2–4

Low-density lipoprotein-cholesterol (LDL-C) has been shown to be a major risk factor in patients with MI, and aggressive LDL-C lowering remains a main target for medical therapy. However, there are still residual risks in MI patients being treated with LDL-C lowering therapy, and this may draw the attention to the prognostic impact of the level of high-density lipoprotein-cholesterol (HDL-C) in acute MI.^5–7

Lipid-lowering therapies are an important component of the early treatment for patients with acute coronary syndromes (ACS), including MI, because randomised-controlled trials have shown that rapid lowering of LDL-C levels with high-intensity statins improves clinical outcomes.^8,9 Reduced levels of HDL-C are a component of the metabolic syndrome, which is associated with an increased risk of cardiovascular events, but the prognostic impact of HDL-C levels has only been studied in patients with stable coronary artery disease, or in those patients at high risk for cardiovascular diseases.^6,10,11

Low HDL-C levels have been shown to be associated with an increased risk of cardiovascular events, but the prognostic impact of low HDL-C levels on clinical outcomes in patients with ACS is still controversial. Moreover, there are no guidelines or recommendations for the treatment or risk stratification of ACS patients with low HDL-C levels.^12,13

Aim

To detect the prognostic impact of the initial level of serum HDL-C on in-hospital major adverse cardiovascular events (MACE), as well as the one-year all-cause mortality in patients presenting with ST-elevation myocardial infarction (STEMI).

Method

A retrospective analysis of the data from 1,415 patients presenting with STEMI in a tertiary-care centre equipped with a 24-hour-ready cardiac catheterisation laboratory in the period from June 2014 to June 2017. We excluded 126 patients who did not have measured HDL-C values recorded during the index hospitalisation, and 242 patients were excluded because they refused consent to collect their data. We also excluded 230 patients who were not taking statin therapy or were lost to follow-up. Follow-up for one-year, regarding all-cause mortality, was done for the included patients.

Fasting peripheral venous blood samples were drawn the next day, after admission to the coronary care unit. Total cholesterol, HDL-C, LDL-C cholesterol, and triglyceride concentrations were measured using the Cobas 8000 modular analyzer series (Roche Diagnostics, Vienna, Austria). Peak high-sensitivity cardiac troponin T (hs-cTnT), troponin I, troponin T, and peak high-sensitivity C-reactive protein (hs-CRP) concentrations were also determined.

Patients were divided into two groups according to HDL-C level. HDL-C level less than 40 mg/dL (2.22 mmol/L) was considered low, while HDL-C level of 40 mg/dL (2.22 mmol/L) or more was considered normal.

The diagnosis of STEMI was based on clinical signs or symptoms of typical angina or angina equivalent symptoms, specific changes on 12-lead electrocardiogram (ECG) (ST-segment elevation in continuous leads or new left bundle branch block), and laboratory changes including increases of serum cardiac biomarkers (creatine kinase-MB, troponin I, or troponin T).

The study was approved by the local ethics committee and all patients signed an informed consent. Retrospective data were retrieved from the electronic database of the hospital. In-hospital data and one-year follow-up data were obtained, including demographics, risk factors, clinical presentation, angiographic data, in-hospital MACE and one-year mortality incidence.

Statistical analysis

The Statistical Package for Social Science (SPSS, Chicago, IL, USA) for Windows, version 22.0 was used for statistical analysis. Continuous variables were expressed as mean ± standard deviation (SD) and compared with Student’s t-test or Mann–Whitney test. Categorical variables were expressed as percentage and compared with Chi-square test. All variables were considered statistically significant when the p value was less than 0.05.

Results

From June 2014 to June 2017, 1,415 patients presenting with STEMI were included and were treated with primary percutaneous coronary intervention (pPCI). All the included patients were taking high-intensity statin therapy (atorvastatin 40–80 mg/day or rosuvastatin 20–40 mg/day). Included patients were divided into two groups according to HDL-C level; HDL-C <40 mg/dL (2.22 mmol/L) was considered low, while HDL-C ≥40 mg/dL was considered normal.

There were 1,109 patients with low HDL-C level, while 306 had a normal HDL-C level, which was statistically significant (p<0.001) (table 1). Patients with normal HDL-C were older, and more likely to be male and/or diabetic; but nothing statistically significant. Patients with low HDL-C had significantly more history of previous ACS (p<0.001). Regarding clinical and angiographic data, anterior STEMI was more prevalent (p<0.001) in patients with low HDL-C, with culprit left anterior descending artery (LAD) during pPCI (table 2).

In-hospital MACCE were significantly lower in patients with normal HDL-C (p=0.03). In-hospital mortality and all-cause mortality at one year were also significantly lower in patients with normal HDL-C (p=0.03 and p=0.01, respectively) (table 2).

Discussion

The main finding in this study was that low HDL-C (<40 mg/dL; 2.22 mmol/L) was associated with higher in-hospital and one-year mortality in STEMI patients. Previous studies have shown controversial data about the prognostic impact of low HDL-C on clinical outcomes in non-ST-segment-elevation acute coronary syndrome (NSTE-ACS) patients, while there is a scarcity of data in STEMI patients.^14–16

Some studies,^17,18 have suggested that sex difference might affect the prognosis of patients with acute MI; however, our results showed that sex difference itself was not statistically different between low and normal HDL-C levels.

Our study provides an important new clinical view on the prognostic significance of cholesterol metabolism in patients with acute STEMI. Our results could highlight, particularly, the prognostic importance of HDL-C status in these patients. Indeed, the prognostic value of low HDL-C level for worse outcomes in STEMI, may emphasise the importance of HDL-C assessment on coronary care unit admission for routine daily clinical and laboratory workup. Above and beyond these prognostic implications, the present results may suggest HDL-C levels as a prophylactic or therapeutic target against the development of adverse cardiovascular events.

Some studies had shown that lower HDL-C levels are associated with a higher risk of cardiovascular events and more burden of atherosclerosis, even among cardiovascular patients with lower LDL-C levels, including those patients treated with statins.^6,11 In our study, we have shown that lower HDL-C levels were associated with a higher risk of adverse outcomes, and appear to correlate with younger age upon presentation in patients with STEMI. In contrast, higher HDL-C levels were associated with older age at presentation in STEMI, which may indicate that higher HDL-C levels delay symptomatic coronary artery disease progression until older age. Nevertheless, lower HDL-C levels appear to be a unique, and potentially modifiable, risk factor for STEMI patients.

Limitations

This was a retrospective study, with the possibility of selection bias or missing data. We could not fully characterise the extent of the metabolic syndrome in our study because waist circumference measures were not routinely collected. There are no specific cut-off values for the cholesterol levels in the Egyptian population, but it was assumed that the Egyptian population level may be similar to those of the Mediterranean region. HDL-C levels before admission were not collected and recorded, HDL-C levels during the hospitalisation may differ from chronic HDL-C levels before presentation, so the impact of low HDL-C levels on the progression of coronary disease may not be accurately represented by in-hospital HDL-C levels.

Conclusion

We can conclude that low HDL-C level was associated with a significantly higher risk of in-hospital and one-year mortality in STEMI patients. Thus, early detection of low HDL-C is important in STEMI patients, and proper treatment with high-intensity statin therapy during the early stage should be considered in STEMI patients with low HDL-C, aiming both to reduce LDL-C levels and increase HDL-C levels.

Key messages

• Low high-density lipoprotein-cholesterol (HDL-C) level is associated with higher risk of in-hospital and one-year mortality in ST-elevation myocardial infarction (STEMI) patients
• Early detection of low HDL-C is important in STEMI patients, and proper treatment with high-intensity statin therapy should be considered in STEMI patients, aiming to reduce LDL-C levels and increase HDL-C levels

Conflicts of interest

None declared.

Funding

None.

Study approval

All procedure aspects were approved by the local ethics committee.

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