Download Prognostic value of LDL to HDL cholesterol ratio in patients

Prognostic value of LDL to HDL cholesterol ratio in patients
undergoing coronary stenting
S. Novo, F. Macaione, E. Corrado, G. Novo, F. Bonura, S. Evola.
Chair of Cardiovascular Disease, Center for the Early Diagnosis of Preclinical and Multifocal Atherosclerosis and for the
Secondary PreventionUniversity Hospital “P. Giaccone” of the University of Palermo – Italy
100
There is overwhelming evidence that an elevated low-density
lipoprotein cholesterol (LDL-C) concentration in plasma is
atherogenic, whereas a higher high-density lipoprotein
cholesterol (HDL-C) level is cardioprotective. A series of studies
suggested that the use of the ratio of LDL-C to HDL-C, which
can be obtained from a standard lipid profile, is superior to the
use of HDL-C or LDL-C alone and that the ratio of LDL-C/HDLC may provide better risk assessment by concurrently
accounting for both atherogenic and protective lipid fractions.
In this work, we mainly clarified whether the LDL-C/HDL-C ratio
would influence long-term clinical outcome in patients after PCI
and evaluated the predictive usefulness of LDL-C/HDLC ratio
after PCI.
Methods
We assessed a population composed of 1300 consecutive
patients with acute coronary syndrome, undergoing
percutaneous coronary intervention (PCI) with implantation of
drug-eluting or bare metal stents from November 2006 and
December 2008 in our Division of Cardiology.
Exclusion criteria were, cardiogenic shock, previous stent in the
target vessel area, coronary artery bypass graft (CABG) within
48 hours of coronary angioplasty, pregnancy, malignant tumor,
life expectancy <1 years, implantation of two different kind of
stent in the same patients, liver dysfunction; familiar
hypercholesterolemia; serum triglycerides (TG) > 400 mg/dl,
left ventricular ejection fraction < 30%. In this manner, a final
sample size of 504 (48.76%) of 1300 patients were enrolled.
Blood lipid profile data were evaluated on venous blood
samples in the fasting state (12 hours) just before percutaneous
coronary intervention (PCI). Total cholesterol (TC), triglycerides
(TG), HDL-c were measured using conventional enzymatic
methods. LDL-c levels were calculated using Freidewald’s
method . After we calculated non-HDL-c, by difference between
total cholesterol (TC) and HDL-c, and LDL-c/HDL-c, TG/HDL-c
and non-HDL-c/HDL-c ratio.
The endpoint was the rate of major adverse cardiac events
(MACE) defined as occurrence of cardiac death, new
hospitalization for ACS (Acute Coronary Syndrome), target
vessel revascularization (TVR) and stroke.
Follow up of clinical end points was conducted for up 3 years
after PCI .
Statistical analysis
Spearman correlation analysis was performed between LDLc/HDL-c ratio and marker of inflammation.
Multivariable logistic regression model with stepwise selection
was used to identify independent factor associated with
outcomes. The areas under the curve (AUC) of the receiver
operating characteristic curves (ROC) were constructed to
assess the degree of predictability of lipids and ratios of interest
on cardiovascular risk.
Table 1 Demographic, clinical, laboratory and angiographic
characteristics of study patients
Mean age (n/SD)
Male n (%)
Smokers n (%)
Previous smokers n (%)
Familiar history of CAD n (%)
Hypertension n (%)
Obesity ( BMI>30Kg/m2)
Diabetes n (%)
Previous CABG n (%)
Previous IMA n (%)
Previous PCI n (%)
Previous HF n (%)
Anemia n (%)
Renal insufficiency n (%)
ACE-Inhibitors n (%)
ARBs n(%)
β blockers n(%)
Statins n(%)
TC (mg/dl)
HDL-c(mg/dl)
LDL-c(mg/dl)
TG (mg/dL)
non-HDL (mg/dL)
L/H ratio
non HDL-c/HDL-c
TG/HDL-c
CRP (mg/dL)
ESR (mm/h)
Fibrinogen (mg/dL)
Emergency Procedure n (%)
Multivessel disease n (%)
Bare metal stent n (%)
N° Stents
Patients with
adverse events
n=179
63.99±11.45
139(77.65)
56(31.28)
52(29.05)
71(39.66)
116(64.80)
33(18.44)
73 (40.78)
15 (8.38)
49 (27.37)
40 (22.35)
11 (6.15)
51 (28.49)
21(11.73)
99 (55.31)
34 (18.99)
119 (66.48)
135 (75.42)
178.25±46.89
42.05±13.25
109.79±40.92
133.26±75.55
136.20±46.30
2.90±1.62
3.63±1.99
3.68±3
2.68±8.70
21.52±19.37
404.74±113.79
30 (16.76)
76 (42.46)
91 (50.84)
1.44±0.65
P
0.78
0.589
0.650
0.291
0.7026
0.104
0.560
0.448
0.542
0.904
0.986
0.958
0.0322
0.520
0.123
0.103
0.348
0.993
0.001
0.013
<0.001
0.919
<0.001
<0.001
<0.001
0.114
0.066
0.208
<0.001
0.991
0.978
0.307
0.848
Patients without
adverse events
n=325
64.27±10.82
244 (75.08)
94(28.92)
79(24.31)
136(41.85)
244(75.08)
52(16)
120 (36.92)
34 (10.46)
92 (28.31)
71 (21.85)
21(6.46)
64 (19.69)
31 (9.54)
156 (48)
84 (25.85)
201 (61.85)
248 (76.31)
165.08±42.37
45.02±12.46
93.55±35.43
132.55±74.30
120.06±39.63
2.19±0.955
2.84±1.184
3.30±2.31
1.56±2.72
18.22±17.13
360.61±98.62
56 (17.23)
139 (42.77)
182 (56)
1.45±0.51
Results
However we searched for possible correlations between LDL-C/
HDL-C ratio and marker of inflammations (data not shown) and
we found a significant correlation with fibrinogen (r = +0.094, p
= 0.034) and CRP (r =+0.14, p = 0.004) concentrations.
There were no significant differences for all other variable and
all three groups did not differ with regard to medications use.
At the end of three years follow up overall MACE were
observed in 22 patients (20.95%) of the LDL-C/HDL-C ≤1.5
group, in 39 patients (27.85%) of the 1.5< LDL-C/HDL-C ≤2.0
group and in 118 patients (45.55%) of the LDL-C/HDL-C >2.0.
(Table 2)
We used logistic regression analysis in order to identify the
independent predictor for occurrence of MACE during follow up.
Multivariate logistic regression analysis was adjusted for all
variables that at univariate analysis showed p value ≤0.10 and
we found that LDL-C/HDL-C ratio (OR 1.593; 95%CI 1.3351.901; p <0.0001) and fibrinogen (OR 1.003; 95%CI 1.0011.005; p = 0.0004) were a significant predictors of MACE after
PCI. (Table 3)
Moreover, the specificity and sensitivity of the correlation
between MACE and blood lipid profile was evaluated using
ROC analysis to assess their predictive value.
The ROC curve analyses showed that the best marker of
MACE was LDL-C/HDL-C ratio, with an area under the ROC
curve of 0.66 (95% CI 0,61- 0,69). (Table 4)
The predictive sensitivity and specificity of the L/H ratio were
75.4% (95%CI 68.4 – 81.5) and 52% (95%CI 46.4 – 57.5),
respectively, for predicting MACE, at the cut-off of 1.85.
Table 2 Incidence of MACE
MACE n (%)
ACS n (%)
Cardiac
Death n (%)
TVR n(%)
Stroke n(%)
LDL/HDL
ratio < 1,5
(n= 105)
LDL/HDl
ratio 1,5-2
(n=140 )
LDL/HDL
ratio>2
(n= 259)
P value
< 0,05
22 (20.95)
39 (27.85)
118 (45.55)
< 0.001
15 (14.28)
1 (0.95)
22 (15.71)
3 (2.14)
69 (26.64)
10 (3.86)
0.006
0.269
5 (4.76)
1 (0.95)
14 (10)
0
36 (13.89)
3 (1.15)
0.032
0.45
Table 3 Logistic regression analysis
The study population consisted of 504 patient with mean age of
65.01 ± 10.85 years, most of the patients were male (75.99%).
The patient sample was divided up into 3 groups: LDL-C/ HDLC ≤1.5 group (Gp1 n= 105), 1.5< LDL-C/HDL-C ≤2.0 group
(Gp2 n= 140), and LDL-C/HDL-C >2.0 groups (Gp3 n= 259).
The groups were different regard to lipid profile, moreover the
patients of Group 3 had significantly higher proportion of
diabetes compared with patients of group 1 and group 2 (p =
0.034). In contrast, in the Group 1 and 2 was a significantly
higher proportion of previous IMA compared with group 3 (p =
0.003).
In addition, among three groups, there was a clear trend for
higher C-reactive protein (CRP) levels and fibrinogen
associated with increasing of LDL-C/ HDL-C ratio, but the
differences did not reach statistical significance.
Variable
Coefficient
Std. Error
Odds ratio
95% CI
0.09012
P
value
<0.05
<0.0001
LDLc/HDL-c
Fibrinogen
0.4660
1.593
0.0009480
0.0004
1.003
1.335
1.901
1.001
1.005
0.003369
LDL-c
LDL/HDL ratio
TC
HDL-c
TG/HDL ratio
TG
non HDL
non HDL/HDL ratio
SE
95% CI
p-value
0.62
0.0262
0.57-0.66
0.0001
0.66
0.58
0.56
0.53
0.508
0.602
0.630
0.0257
0.0266
0.0267
0.0270
0.0273
00265
0.0261
0.61-0.69
0.54-0.62
0.52-0.61
0.49-0.57
0.46-0.55
0.56-0.64
0.58-0.67
0.0001
0.0023
0.0102
0.2056
0.7574
0.0001
0.0001
60
40
LDL
LDL-c/HDL-c
non HDL-c/HDL-c
20
0
0
20
40
60
100-Specificity
100
Figure 1 Comparison receiver operating characteristic (ROC)
curves with AUC > 0. 60.
Conclusion
This study showed that the three groups were significant
different about lipid profile and ratios but that only LDL-C/HDLC ratio was significant predictor of occurrence of MACE in
patient undergoing PCI, on long term outcome after PCI. From
multivariate analysis came up from, too, that the fibrinogen was
an important predictor for MACE. Another very interesting
aspect was that, after comparison the area under the ROC
curve, built only for lipid profile, the area under the ROC curve
was largest for the LDL-c/HDL-c ratio, than that for another
lipids and lipid ratios. Especially, after the receiver operating
characteristic (ROC) curve analysis, the cut-off point of LDLC/HDL-C ratio to identifying of occurrence of MACE, was ≥1.85.
In conclusion, pending further studies to confirm these results,
in light of these data, it would be important to be able to better
define the role of to assess if pre-procedural risk stratification
with lipid ratio of LDL-c/HDL-c might be used as an integrated
and simple lipid measure to the risk of adverse events after
PCI, so as secondary prevention as an adjunct to established
clinical risk factors may be useful as form of prevention for early
identification of high risk patients for MACE, and a better
understanding the relationship between the LDL-c/HDL-c ratio
and fibrinogen is needed. Research now in progress will almost
certainly help clarify the picture.
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Declaration of interest: There is no conflict of interest
with any financial organization regarding the material
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References
Table 4 Comparison of areas under the ROC curves (95% CI) for
blood lipid regard to MACE
AUC
80
Sensitivity
Purpose