Open Access

Impact of low high-density lipoprotein-cholesterol level on 2-year clinical outcomes after acute myocardial infarction in patients with diabetes mellitus

  • Hyung Joon Joo1,
  • Sang-A Cho1,
  • Soon Jun Hong1,
  • Seung-Ho Hur2,
  • Jang-Ho Bae3,
  • Dong-Ju Choi4,
  • Young-Keun Ahn5,
  • Jong-Seon Park6,
  • Rak-Kyeong Choi7,
  • Donghoon Choi8,
  • Joon-Hong Kim9,
  • Kyoo-Rok Han10,
  • Hun-Sik Park11,
  • So-Yeon Choi12,
  • Jung-Han Yoon13,
  • Hyeon-Cheol Kwon14,
  • Seung-Woon Rha15,
  • Kyung-Kuk Hwang16,
  • Kyung-Tae Jung17,
  • Seok-Kyu Oh18,
  • Jae-Hwan Lee19,
  • Eun-Seok Shin20,
  • Kee-Sik Kim21,
  • Hyo-Soo Kim22Email author and
  • Do-Sun Lim1Email author
Contributed equally
Lipids in Health and Disease201615:197

https://doi.org/10.1186/s12944-016-0374-5

Received: 12 September 2016

Accepted: 11 November 2016

Published: 18 November 2016

Abstract

Background

It is still unclear whether low high-density lipoprotein cholesterol (HDL-C) affects cardiovascular outcomes after acute myocardial infarction (AMI), especially in patients with diabetes mellitus.

Methods

A total of 984 AMI patients with diabetes mellitus from the DIabetic Acute Myocardial InfarctiON Disease (DIAMOND) Korean multicenter registry were divided into two groups based on HDL-C level on admission: normal HDL-C group (HDL-C ≥ 40 mg/dL, n = 519) and low HDL-C group (HDL-C < 40 mg/dL, n = 465). The primary endpoint was 2-year major adverse cardiovascular events (MACE), defined as a composite of cardiac death, non-fatal myocardial infarction (MI), and target vessel revascularization (TVR).

Results

The median follow-up duration was 730 days. The 2-year MACE rates were significantly higher in the low HDL-C group than in the normal HDL-C group (MACE, 7.44% vs. 3.49%, p = 0.006; cardiac death, 3.72% vs. 0.97%, p = 0.004; non-fatal MI, 1.75% vs. 1.55%, p = 0.806; TVR, 3.50% vs. 0.97%, p = 0.007). Kaplan-Meier analysis revealed that the low HDL-C group had a significantly higher incidence of MACE compared to the normal HDL-C group (log-rank p = 0.013). After adjusting for conventional risk factors, Cox proportional hazards analysis suggested that low HDL-C was an independent risk predictor for MACE (hazard ratio [HR] 3.075, 95% confidence interval [CI] 1.034-9.144, p = 0.043).

Conclusions

In patients with diabetes mellitus, low HDL-C remained an independent risk predictor for MACE after adjusting for multiple risk factors during 2-year follow-up of AMI.

Trial registration

This study was the sub-analysis of the prospective multi-center registry of DIAMOND (Diabetic acute myocardial infarction Disease) in Korea. This is the observational study supported by Bayer HealthCare, Korea. Study number is 15614. First patient first visit was 02 April 2010 and last patient last visit was 09 December 2013.

Keywords

High-density lipoprotein cholesterol Major adverse cardiovascular events Acute myocardial infarction Diabetes mellitus

Background

Acute myocardial infarction (AMI) is a leading cause of mortality in patients with diabetes mellitus. Recent data revealed a 10–15% 1-year mortality rate after AMI in a diabetic population [1]. Korean data also showed a higher mortality rate after AMI in diabetic patients compared to non-diabetic patients [2]. Preventive strategies targeting platelet activity and lipid profiles in addition to glycemic control and lifestyle modification are an essential part of management in these patients [3, 4].

Previous primary prevention trials revealed that low high-density lipoprotein cholesterol (HDL-C) level is a significant risk factor for cardiovascular events in the general population [5, 6]. The Treating to New Targets (TNT) study revealed that approximately 15% of patients with diabetes mellitus have low HDL-C level [7]. In diabetes, insulin resistance increases triglyceride-enriched HDL particles and causes more rapid clearance of HDL particles [8]. Thus, low HDL-C is more common in diabetic patients. Moreover, previous epidemiologic studies demonstrated a higher prevalence of low HDL-C in the Asian population [9, 10]. The association between low HDL-C and coronary heart disease seemed to be stronger in the Asian population compared to non-Asians [11].

Recently, low HDL-C levels have been reportedly associated with a higher rate of cardiovascular events in patients with stable coronary artery disease, percutaneous coronary intervention, or even AMI [1214]. However, it is still controversial whether low HDL-C affects cardiovascular outcomes after AMI. In addition, no studies have evaluated AMI patients with diabetes mellitus. In the present study, we have investigated the prevalence of low HDL-C and its long-term clinical impact in diabetic patients after AMI.

Methods

Study design

The DIAMOND (DIabetic Acute Myocardial infarctiON Disease registry in Korea) study was a multicenter, prospective observational study [15]. Briefly, between April 2010 and December 2013, 1,198 diabetic patients admitted for AMI were enrolled at 22 institutions in South Korea. The study participants were encouraged to follow up at 1, 6, 12, and 24 months after discharge. The study was approved by the institutional review board of each institute and performed in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from all patients.

The present study was a retrospective analysis of previously collected data that were locked at December 2014. During the follow-up period, 6 patients withdrew consent, 79 never followed up after discharge, and 129 had missing values for laboratory findings on admission. Finally, 984 patients were analyzed.

Definitions

AMI was defined based on elevated cardiac troponin-I or T level (exceeding upper limit of normal) or creatine kinase-MB fraction (CK-MB) (exceeding three times upper limit of normal), along with angiographic evidence. Angiographic evidence for AMI included significant coronary stenosis, i.e., more than 50% luminal stenosis, intracoronary filling defect or haziness suggesting coronary thrombus/vulnerable plaque, or coronary artery vasospasm confirmed by intracoronary acetylcholine or ergonovine provocation test. Diabetes mellitus was defined by fasting plasma glucose level on two separate occasions ≥ 126 mg/dL, a random plasma glucose level ≥ 200 mg/dL, 2-h plasma glucose post-75 g dextrose load on two separate occasions ≥ 200 mg/dL, or taking oral hypoglycemic agents or using insulin. Dyslipidemia was defined as total cholesterol level ≥ 240 mg/dL, low-density lipoprotein cholesterol (LDL-C) level ≥ 130 mg/dL, HDL-C level < 40 mg/dL, triglyceride level ≥ 150 mg/dL, and/or treatment with lipid lowering agents. Low HDL-C was defined as < 40 mg/dL. Renal function was estimated with the glomerular filtration rate (eGFR), which was calculated with the Modification of Diet in Renal Disease (MDRD) equation as following: eGFR (mL/min/1.73 m2) = 175 × (serum creatinine level)-1.154 × (age)-0.203 × (0.742 if female) [16].

Endpoint

In the present analysis, major adverse cardiac events (MACE) was defined as a composite of cardiac death, non-fatal myocardial infarction (MI), and target vessel revascularization (TVR). Revascularization other than TVR (non-TVR) was also analyzed. Definite stent thrombosis was assessed according to the Academic Research Consortium definition.

Statistical analysis

Categorical variables were reported as count (percentage) and continuous variables as the mean ± standard deviation. Comparisons between two groups were performed using the independent Student’s t-test for continuous variables, and the χ2 test for categorical variables. Kaplan–Meier survival curves with a log-rank test and Cox proportional hazard model analyses were performed to compare the long-term incidence of MACE and cardiac death between the two groups. The univariate and multivariate Cox proportional hazard regression analyses were used to identify risk predictors for MACE and cardiac death. The risk factors were tested with the multivariate Cox proportional hazard regression model by the backward selection method. The candidate variables for the model included HDL-C level, age, men, body mass index (BMI), current smoking, previous MI, ST-segment elevation myocardial infarction (STEMI) on admission, primary percutaneous coronary intervention (PCI), hypertension, statin use, estimated glomerular filtration rate (eGFR), hemoglobin A1c (HbA1c) level, high-sensitivity C-reactive protein (hsCRP) level, LDL-C level, left ventricular ejection fraction (LVEF), multivessel disease, lesion type (B2/C), stent diameter ≤ 2.75 mm, and stent length ≥ 28 mm. The selection significance level was 0.1. The results were expressed as the hazard ratio (HR) with a 95% confidence interval (CI) and p-value. All tests were two-tailed, and p-values less than 0.05 were considered statistically significant. All statistical analyses were performed using SAS (v. 9.3, SAS Institute Inc., USA).

Results

Among a total of 984 diabetic patients who experienced AMI, 465 patients (47.3%) were in the low HDL-C group. Baseline clinical characteristics are summarized in Table 1. The low HDL-C group had more men (p = 0.002). There were fewer patients with newly diagnosed diabetes mellitus in the low HDL-C group (p = 0.034). Laboratory findings showed lower total cholesterol and higher triglyceride levels in the low HDL-C group (p < .001). Angiographic findings showed no significant difference between the two groups (Table 2).
Table 1

Baseline clinical characteristics

 

Low HDL (n = 465)

Normal HDL (n = 519)

p-value

Age (years)

64.12 ± 9.91

65.10 ± 9.78

0.120

Male, n (%)

328 (70.54)

318 (61.27)

0.002

BMI (kg/m2)

24.23 ± 3.01

24.06 ± 3.02

0.301

Smoking, n (%)

164 (35.42)

166 (31.98)

0.255

Newly diagnosed DM, n (%)

30 (6.45)

53 (10.21)

0.034

Hypertension, n (%)

302 (65.09)

335 (64.92)

0.957

Dyslipidemia, n (%)

115 (24.78)

149 (28.76)

0.160

Previous MI, n (%)

28 (6.02)

33 (6.36)

0.827

On Admission

 STEMI, n (%)

217 (46.67)

254 (48.94)

0.476

 Primary PCI, n (%)

280 (60.22)

318 (61.27)

0.735

 LVEF, n (%)

50.51 ± 12.31

51.00 ± 11.26

0.522

 Total cholesterol (mg/dL)

162.92 ± 45.74

180.83 ± 44.34

<.001

 Triglyceride (mg/dL)

151.59 ± 109.69

121.63 ± 83.35

<.001

 LDL-C (mg/dL)

100.97 ± 34.76

105.63 ± 45.82

0.072

 HDL-C (mg/dL)

32.70 ± 5.22

53.8 ± 26.83

<.001

 Creatinine (mg/dL)

2.16 ± 16.55

1.69 ± 11.84

0.611

 HbA1c (%)

7.83 ± 1.58

7.66 ± 1.49

0.111

 hsCRP (mg/L)

6.00 ± 15.69

6.01 ± 24.07

0.993

 Peak CK-MB (ng/mL)

75.71 ± 120.75

85.67 ± 122.03

0.202

 Maximum Troponin-I (ng/mL)

28.76 ± 55.53

29.71 ± 58.47

0.825

Medication at discharge

 Aspirin, n (%)

449 (98.25)

510 (98.84)

0.442

 Clopidogrel, n (%)

434 (94.97)

487 (94.38)

0.684

 Cilostazol, n (%)

88 (19.26)

105 (20.35)

0.670

 Beta blocker, n (%)

394 (85.65)

437 (84.36)

0.573

 ACEI/ARB, n (%)

376 (81.74)

441 (85.14)

0.153

 Statin, n (%)

381 (82.83)

452 (87.26)

0.052

 Nitrate, n (%)

128 (27.83)

149 (28.76)

0.745

 Insulin, n (%)

76 (16.52)

70 (13.51)

0.188

Data are presented as mean ± SD for continuous variables and numbers (%) for categorical variables. BMI body mass index, DM diabetes mellitus, MI myocardial infarction, STEMI ST-segment elevation MI, PCI percutaneous coronary intervention, LVEF left ventricular ejection fraction, LDL-C low-density lipoprotein cholesterol, HDL-C high-density lipoprotein cholesterol, HbA1c hemoglobin A1c, hsCRP high-sensitivity C-reactive protein, CK-MB creatine kinase-MB, ACEI angiotensin-converting enzyme inhibitor, ARB angiotensin II receptor blocker

Table 2

Angiographic and procedural characteristics

 

Low HDL

Normal HDL

p-value

Target vessel, n (%)

   

 Left main

14 (3.01)

11 (2.12)

0.375

 LAD

224 (48.17)

270 (52.02)

0.228

 LCX

114 (24.52)

144 (27.75)

0.250

 RCA

175 (37.63)

178 (34.30)

0.276

Multivessel disease, n (%)

284 (61.08)

302 (58.19)

0.357

Type B2/C lesion, n (%)

371 (84.9)

403 (80.76)

0.095

TIMI grade, n (%)

   

 0

187 (42.79)

190 (38.08)

0.404

 1

52 (11.90)

64 (12.83)

 

 2

46 (10.53)

78 (15.63)

 

 3

152 (34.78)

167 (33.47)

 

Drug-eluting stent, n (%)

398 (98.76)

445 (97.8)

0.294

Stent diameter (mm)

3.10 ± 0.45

3.13 ± 0.44

0.215

Stent length (mm)

25.44 ± 8.25

24.71 ± 9.12

0.272

Stent number

1.57 ± 0.89

1.55 ± 0.82

0.722

Data are presented as mean ± SD for continuous variables and numbers (%) for categorical variables. LAD left anterior descending artery, LCX left circumflex artery, RCA right coronary artery

In-hospital and 2-year clinical outcomes are shown in Table 3. There were no significant differences in in-hospital deaths and complications between the two groups. The 2-year clinical outcomes were accessed in the remaining 973 patients after excluding the patients with in-hospital death. Median follow-up period was 730 days. During the follow-up period, the incidence of MACE, cardiac death, and TVR was significantly higher in the low HDL-C group (MACE, 7.44% vs. 3.49%, p = 0.006; cardiac death, 3.72% vs. 0.97%, p = 0.004; non-fatal MI, 1.75% vs. 1.55%, p = 0.806; TVR, 3.50% vs. 0.97%, p = 0.007). Kaplan-Meier analysis revealed that the low HDL-C group had a significantly higher incidence of MACE and cardiac death compared to the normal HDL-C group (MACE, log-rank p = 0.012; cardiac death, log-rank p = 0.005; Fig. 1).
Table 3

In-hospital and 2-year clinical outcomes after acute myocardial infarction

 

Low HDL

Normal HDL

p-value

In-hospital

 Death

8 (1.72)

3 (0.58)

0.089

 Cardiogenic shock

10 (2.15)

6 (1.16)

0.218

 Acute renal failure

5 (1.08)

2 (0.39)

0.199

 Major bleeding

4 (0.86)

6 (1.16)

0.644

During follow-up period

 MACE

34 (7.44)

18 (3.49)

0.006

 Cardiac death

17 (3.72)

5 (0.97)

0.004

 Non-fatal MI

8 (1.75)

8 (1.55)

0.806

 TVR

16 (3.50)

5 (0.97)

0.007

 Non-TVR

11 (2.41)

12 (2.33)

0.934

 Stent thrombosis, definite

3 (0.65)

1 (0.19)

0.266

Data are presented as numbers (%) for categorical variables. MACE major adverse cardiac event, MI myocardial infarction, TVR target vessel revascularization

Fig. 1

Kaplan-Meier analysis of low HDL-C and normal HDL-C groups. a cumulative MACE-free survival. b cumulative cardiac death-free survival. HR, hazard ratio; 95% CI, 95% confidence interval; Ref, reference

In multivariable Cox proportional hazard model analyses, HDL-C level, BMI, hypertension, and eGFR were independent significant predictors for MACE [HDL-C, HR (95% CI) 0.95 (0.905 - 0.999), p = 0. 047; BMI, HR (95% CI) 0.84 (0.714 – 0.993), p = 0.041; hypertension, HR (95% CI) 4.80 (1.052 – 21.927), p = 0.043; eGFR, HR (95% CI) 0.981 (0.966 – 0.996), p = 0.016] after adjusting for conventional risk factors (Table 4). LVEF remained the only independent predictor for cardiac death [HR (95% CI) 0.893 (0.828 – 0.964), p = 0.004].
Table 4

Univariate and multivariate analysis for risk factors to predict MACE and cardiac death

 

MACE

Cardiac death

Risk Factor

β

HR (95% CI)

p-value

β

HR (95% CI)

p-value

Univariate analysis

 Age

0.04

1.04 (1.007 – 1.066)

0.014

0.10

1.10 (1.048 – 1.158)

<0.001

 Male

−0.10

0.90 (0.513 – 1.588)

0.723

−0.33

0.72 (0.306 – 1.677)

0.443

 BMI

−0.02

0.98 (0.895 – 1.073)

0.666

−0.20

0.82 (0.703 – 0.947)

0.008

 Current Smoking

−0.41

0.66 (0.354 – 1.243)

0.200

−0.56

0.57 (0.210 – 1.543)

0.268

 Previous MI

−0.55

0.58 (0.327 – 1.026)

0.061

−0.92

0.40 (0.157 – 1.023)

0.056

 Hypertension

1.67

5.31 (2.113 – 13.363)

<0.001

1.26

3.51 (1.038 – 11.858)

0.043

 HDL-C

−0.05

0.95 (0.928 – 0.981)

0.001

−0.08

0.92 (0.879 – 0.963)

<0.001

 LDL-C

−0.01

0.99 (0.986 – 1.001)

0.098

−0.01

1.00 (0.983 – 1.007)

0.395

 eGFR

−0.02

0.99 (0.977 – 0.994)

0.001

−0.03

0.973 (0.960 – 0.986)

<0.001

 Hba1c

0.02

1.02 (0.852 – 1.231)

0.802

0.13

1.14 (0.880 – 1.482)

0.319

 hsCRP

0.002

1.00 (0.988 – 1.017)

0.786

0.003

1.00 (0.985 – 1.022)

0.739

 STEMI at admission

−0.55

0.58 (0.327 – 1.026)

0.061

−0.92

0.40 (0.157 – 1.023)

0.056

 Primary PCI

−0.38

0.685 (0.397 – 1.183)

0.175

−1.27

0.28 (0.115 – 0.693)

0.006

 MVD

0.13

1.14 (0.649 – 2.008)

0.647

−0.22

0.80 (0.347 – 1.859)

0.608

 Lesion type (B2/C)

0.05

1.05 (0.466 – 2.346)

0.914

−0.60

0.55 (0.175 – 1.727)

0.306

 Stent diameter ≤2.75 mm

0.02

1.02 (0.490 – 2.124)

0.958

−1.27

0.28 (0.035 - 2.211)

0.227

 Stent length ≥28 mm

0.49

1.64 (0.842 – 3.174)

0.146

0.41

1.51 (0.437 – 5.209)

0.516

 LVEF

−0.04

0.96 (0.941 – 0.986)

0.002

−0.10

0.904 (0.870 – 0.939)

<0.001

 Statin at discharge

−0.35

0.71 (0.354 – 1.407)

0.322

−0.83

0.44 (0.170 – 1.113)

0.083

Multivariate analysis

 HDL-C

−0.05

0.95 (0.905 - 0.999)

0.047

-

-

-

 Age

−0.05

0.96 (0.906 – 1.006)

0.085

-

-

-

 BMI

−0.17

0.84 (0.714 – 0.993)

0.041

−0.31

0.73 (0.537 – 1.002)

0.051

 Hypertension

1.57

4.80 (1.052 – 21.927)

0.043

-

-

-

 eGFR

−0.02

0.981 (0.966 – 0.996)

0.016

−0.02

0.98 (0.954-1.004)

0.093

 Stent diameter ≤2.75 mm

-

-

-

−1.81

0.16 (0.017 – 1.587)

0.119

 LVEF

-

-

-

−0.11

0.893 (0.828 – 0.964)

0.004

MACE major adverse cardiovascular events, HR hazard ratio, 95% CI 95% confidence interval, BMI body mass index, MI myocardial infarction, LDL-C low-density lipoprotein cholesterol, eGFR estimated glomerular filtration rate, hsCRP high-sensitivity C-reactive protein, STEMI ST-segment elevation myocardial infarction, PCI percutaneous coronary intervention, MVD multi-vessel disease, LVEF left ventricular ejection fraction, n.d. not determined

Next, the unadjusted HRs for MACE were calculated in various subgroups based on age, sex, BMI, smoking, HbA1c, LDL-C, creatinine, and LVEF (Fig. 2). Interestingly, statistical significance was found in patients with high BMI. There were no significant interactions between HDL-C and MACE among the other 7 subgroups.
Fig. 2

Comparative unadjusted hazard ratios of MACE for subgroups. MACE, major adverse cardiovascular events; 95% CI, 95% confidence interval; BMI, body mass index; LDL-C, low-density lipoprotein cholesterol; LVEF, left ventricular ejection fraction

Discussion

The main findings of the present study are as follows: (1) 46.2% of diabetic patients presenting with AMI had a low HDL-C level; (2) 2-year clinical outcomes including MACE (mainly cardiac death and TVR) were poorer in diabetic patients with a low HDL-C level after AMI compared to those with a normal HDL-C level; (3) low HDL-C level remained an important risk predictor for MACE after adjusting for confounding clinical factors.

Previous community-based primary prevention studies showed that low HDL-cholesterol level was strongly associated with poor cardiovascular outcome in the general population [17, 18]. Current guidelines strongly recommend statin therapy for patients with overt atherosclerotic vascular diseases and diabetes mellitus [19, 20]. A previous study demonstrated that statin therapy increased HDL-C level by approximately 7.5%, and was associated with coronary atherosclerotic regression [21]. However, more than 40% of statin-treated patients have a persistently low HDL-C level [22, 23]. Several studies also suggested low HDL-C as an independent risk predictor, even in patients with overt atherosclerotic vascular diseases on statin therapy. Seo et al. reported that a low HDL-C level on statin therapy was associated with poor clinical outcome after PCI [12]. Ogital et al. also showed that low HDL-C was a risk factor in diabetic patients with stable coronary artery disease [13]. Recently, Lee et al. showed similar results in patients with AMI [14]. The present study showed a higher MACE rate in diabetic AMI patients with low HDL-C level compared to those with a normal HDL-C level.

On the other hand, several studies have questioned the impact of HDL-C on cardiovascular prognosis. Izuhara et al. showed that the statistical significance of low HDL-C in poor clinical outcomes disappeared after adjusting for confounding factors in patients who underwent PCI [23]. Angeloni et al. showed similar 3-year MACE rates in low and high HDL-C groups, even in patients who underwent coronary artery bypass grafting [24]. Ji et al. also showed no significant difference in 1-year MACE rates between the two groups in AMI patients [25].

The discrepancy among studies might be explained by several factors. First, the studies were performed in different clinical settings and had different demographic and risk profiles. The clinical situations could have affected the anti-atherogenic and anti-inflammatory function of HDL-C. Recently, many studies have focused on the function of HDL-C rather than the level. HDL-C plays an important role in atherogenesis through reverse cholesterol transport. Removing cholesterol from macrophages (called “macrophage cholesterol efflux”) is significantly associated with cardiovascular events [26, 27]. Cholesterol efflux capacity and the NO-producing effect of HDL-C were also decreased in patients with acute coronary syndrome [28, 29]. Dysfunction of HDL-C was also reported in diabetic patients [30]. These findings suggested that HDL-C dysfunction might mask the clinical significance of serum HDL-C level for cardiovascular prognosis depending on the clinical situation. In other words, the quality of HDL-C might be more significant than the quantity in selected populations. Second, the cut-off value of HDL-C could affect the results of clinical studies. Interestingly, the studies using the cut-off value of 40 mg/dL suggested that low HDL-C was an independent risk predictor [1214]. Other studies using different cut-off values for men and women (40 mg/dL for men and 50 mg/dL for women) failed to show the significance of low HDL-C [2325]. More importantly, 2 studies from the same AMI registry showed different results. One adopted the cut-off value of 40 mg/dL for both men and women [14], and the other study used different cut-off values for men and women (40 mg/dL for men and 50 mg/dL for women) [25]. In the present study, receiver operating characteristic (ROC) curves of HDL-C for cardiac death showed that the area under the curve (AUC) for men was 0.722 and 0.753 for women (Additional file 1: Figure S1); optimal cut-off points with the Youden index were 38 mg/dL for men and 35 mg/dL for women. ROC curves of HDL-C for MACE showed that the AUC for men was 0.634 and 0.660 for women; optimal cut-off points with the Youden index were 38 mg/dL for men and 40 mg/dL for women. Thus, we used the same cut-off value of 40 mg/dL for both men and women. Moreover, 2015 Korean guidelines for the management of dyslipidemia adopted a criterion of below 40 mg/dL as low HDL-C for both men and women [31].

A genetic mechanism reportedly links low HDL-C and inflammatory states [32]. Hoven et al. also showed a clinical relationship between low HDL-C level and its inflammatory and oxidative phenotype [33]. Moreover, there is much experimental evidence for the beneficial effects of HDL-C [34]. Although previous clinical trials aimed at raising HDL-C failed to show promising results [3538], new HDL-C-based strategies designed to improve HDL-C functionality instead of increasing the HDL-C level have been under development [39, 40].

There are several limitations. First, the study subjects were divided into only 2 groups. We did not address the impact of the other ranges of HDL-C level (e.g., HDL-C > 70 mg/dL or < 20 mg/dL) due to the limited patient numbers. Thus, the possible protective role of high HDL-C level or its dose–response relationship could not be investigated. Second, the current guidelines recommend statin therapy for diabetic patients regardless of their lipid profile [31, 41]. Detailed information (name and dose) on statins and other medications affecting HDL-C levels were not assessed. However, the effect of statins on HDL-C has been known to be relatively small. Moreover, our data highlighted the clinical limitations of current statin usage and proposed HDL-C as a therapeutic target despite the failures of previous trials. Third, the follow-up rate of HDL-C was only 62.0% in the present study. Data on HDL-C levels before admission were not obtained. Thus, we cannot analyze the dynamics of HDL-C. Fourth, serum uric acid level was not included and adjusted for a potential confounding factor. Although the relationship between serum uric acid level and the prognosis of acute myocardial infarction has been still controversial, serum uric acid level is a well-known surrogate marker for inflammation and atherosclerosis [42]. Unfortunately, serum uric acid level was not available in our registry. Additional data including serum uric acid level and other inflammatory biomarkers could be more informative to understanding the clinical impact of HDL-C.

Conclusions

The 2-year incidence of MACE, cardiac death, and TVR was significantly higher in diabetic patients with a low HDL-C level compared to those with a normal HDL-C level after AMI. Low HDL-C level remained an independent risk predictor for both MACE and cardiac death after adjusting for multiple risk factors.

Abbreviations

AMI: 

Acute myocardial infarction

AUC: 

Area under the curve

BMI: 

Body mass index

CI: 

Confidence interval

CKD: 

Chronic kidney disease

CK-MB: 

Creatine kinase-MB fraction

DIAMOND: 

DIabetic acute myocardial InfarctiON disease

HbA1c: 

Hemoglobin A1c

HDL-C: 

High-density lipoprotein cholesterol

HR: 

Hazard ratio

hsCRP: 

High-sensitivity C-reactive protein

LDL-C: 

Low-density lipoprotein cholesterol

LVEF: 

Left ventricular ejection fraction

MACE: 

Major adverse cardiovascular events

MI: 

Myocardial infarction

PCI: 

Percutaneous coronary intervention

ROC: 

Receiver operating characteristic

STEMI: 

ST-segment elevation myocardial infarction

TNT: 

Treating to new targets

TVR: 

Target vessel revascularization

Declarations

Acknowledgements

This study was supported by a grant from Bayer Korea, Co., Ltd.

Funding

This study was supported by a grant from Bayer Korea, Co., Ltd. It was also mentioned on the Acknowledgements section.

Availability of data and materials

Not applicable.

Authors’ contributions

HJJ researched data and worte the manuscript. S.C. analyzed data. SJH, SH, JB, DC, YA, JP, RC, DC, JK, KH, HP, SC, JY, HK, SR, KH, KJ, SO, JL, ES, and KK collected and reviewed the data. HK and DL reviewed the manuscript and contributed to discussion. All authors read and approved the final manuscript.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

All authors have read and approved the submission and publication of this manuscript.

Ethics approval and consent to participate

The study was approved by the institutional review board of each institute and performed in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from all patients.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Division of Cardiology, Korea University Anam Hospital
(2)
Division of Cardiology, Keimyung University Dongsan Medical Center
(3)
Division of Cardiology, Konyang University Hospital
(4)
Division of Cardiology, Seoul National University Bundang Hospital
(5)
Division of Cardiology, Chonnam National University Hospital
(6)
Division of Cardiology, Yeungnam University Hospital
(7)
Division of Cardiology, Sejong General Hospital
(8)
Division of Cardiology, Yonsei University Severance Hospital
(9)
Division of Cardiology, Pusan National University Yangsan Hospital
(10)
Division of Cardiology, Hallym University Kangdong Sacred Heart Hospital
(11)
Division of Cardiology, Kyungpook National University Hospital
(12)
Division of Cardiology, Ajou University Hospital
(13)
Division of Cardiology, Wonju Severance Christian Hospital
(14)
Division of Cardiology, Samsung Medical Center
(15)
Division of Cardiology, Korea University Guro Hospital
(16)
Division of Cardiology, Chungbuk National University Hospital
(17)
Division of Cardiology, Eulji University Hospital
(18)
Division of Cardiology, Wonkwang University Hospital
(19)
Division of Cardiology, Chungnam National University Hospital
(20)
Division of Cardiology, Ulsan University Hospital
(21)
Division of Cardiology, Daegu Catholic University Medical Center
(22)
Division of Cardiology, Seoul National University Hospital

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Copyright

© The Author(s). 2016

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