epidemiological data have demonstrated that low levels of highdensity lipoprotein cholesterol ( hdlc ) are a strong and independent predictor of cardiovascular disease . however , the clinical interaction between hdlc and lowdensity lipoprotein cholesterol ( ldlc ) level , especially the predictive value of hdlc in patients treated with statins or with low ldlc levels , is not well characterized .
because hdlc may be a potential therapeutic target for considerable residual risk in patients who reached a very low ldlc level , it is important to evaluate the association between hdlc and cardiovascular risk among patients with low ldlc levels .
percutaneous coronary intervention ( pci ) is frequently accompanied by cardiac marker elevation after the procedure ( also known as periprocedural myocardial injury ) , especially with the use of highsensitivity troponin .
a large body of data demonstrated that postprocedural troponin elevation was associated with a worse clinical outcome .
the study by sattler showed that high hdlc was associated with reduced risk for periprocedural myocardial infarction , which is defined as elevation of postprocedural cardiac troponin above 3 times upper limit of normal ( uln ) .
no data exist about the association of hdlc with periprocedural myocardial infarction or injury following elective pci across a range of ldlc levels . therefore
, the objective of this study was to assess the association of hdlc with periprocedural myocardial injury following elective pci across a range of ldlc levels , especially in patients with ldlc < 70 mg / dl in a large cohort of chinese population from a single center .
between december 2010 and december 2012 , 2646 consecutive patients with normal levels of cardiac troponin i ( ctni ) and creatine kinasemb ( ckmb ) and without acute myocardial infarction in the past 4 weeks who attempted to undergo elective pci at our center were eligible for this study . of these patients , 96 patients were excluded because a total chronic occlusion could not be crossed with a wire ; 2 patients were excluded because a subtotal chronic occlusion could not be crossed with a wire ; 4 patients were excluded because a severely calcified or tortuous lesion could not be crossed with a balloon ; 10 patients were excluded because they were treated with atheroablative , distal protection devices , or aspiration thrombectomy ; and 5 patients were excluded because of residual stenosis more than 50% with angioplasty only .
angiographic success of pci was defined as residual stenosis < 20% with stenting and residual stenosis
unstable angina was defined as rest angina , newonset severe angina , and increasing angina within 2 months .
secondly , postprocedural ctni > 3uln , which was the diagnosis criteria of periprocedural myocardial infarction published in 2007 , and postprocedural ctni > 5uln , which was a requirement in the arbitrarily revised diagnosis criteria published in 2012 , were also examined in this study .
this study was approved by the ethics committee of fuwai hospital , complied with the declaration of helsinki , and all patients gave their informed consent for participation in this study .
the indication for pci was based on the american college of cardiology / american heart association recommendations and was performed by experienced interventional cardiologists . before the procedure
, all patients without contraindications received aspirin 100 mg daily or a loading dose of 300 mg , depending on whether daily aspirin therapy was already taken , and received clopidogrel 75 mg daily or a loading dose of 300 mg , depending on whether daily longterm clopidogrel therapy was already taken prior to intervention .
all patients received either 5000 u or 70 u / kg bolus of unfractionated heparin just before the procedure , and an additional bolus of 2000 to 3000 u was given every hour if the procedure lasted for > 1 hour .
vascular access and pci type ( angioplasty only , angioplasty and stenting , or primary stenting ) were determined by the interventional cardiologist according to the patient characteristics .
total balloon inflation times and inflation pressures were determined by the interventional cardiologist according to the technical properties of the balloon and the stent . after the procedure , all patients continued with aspirin and clopidogrel therapy daily .
use of glycoprotein iib / iiia receptor antagonists or anticoagulants was at the discretion of the interventional cardiologist . in all patients ,
a 12lead ecg was recorded before , immediately after pci , and in the case of the occurrence of symptoms that were interpreted as a postprocedural ischemic event .
the hdlc concentration was determined by a homogeneous method ( determiner l hdl , kyowa medex , tokyo ) with a coefficient of variation of < 5% and a total imprecision of < 10% .
the ldlc concentration was analyzed by selective solubilization method ( ldlc test kit , kyowa medex , tokyo ) with a coefficient of variation of < 5% and a total imprecision of < 10% .
ctni levels were determined in venous blood samples before pci , 24 hours after pci , and in the event of the occurrence of symptoms or signs suggestive of myocardial ischemia .
ctni was analyzed by an immunochemiluminometric assay ( access accutni , beckman coulter , ca ) .
the uln was defined as the 99th percentile of normal population with a total imprecision of < 10% .
the uln of this test was 0.04 ng / ml . the ckmb activity was determined before pci by an immunoinhibition assay ( creatine kinasemb kit , biosino , beijing ) with a uln of 24 u / l .
data are presented as meansd , median with interquartile ranges , or frequencies with percentages , as appropriate .
comparisons among groups were made with analysis of variance ,  test , fisher 's exact test , or kruskal  wallis test as appropriate .
univariate linear regression analyses were performed to determine the association between clinical parameters and postprocedural ctni levels .
variables with a p value < 0.1 in the univariate linear regression were entered into a stepwise multivariable linear model to determine the independent association between clinical parameters and postprocedural ctni levels .
logistic regression analyses were performed to determine the relationship of hdlc with the occurrence of postprocedural ctni elevations above various multiples of uln .
logistic models were adjusted for variables independently associated with postprocedural ctni levels . additionally , a separate model adjusting for variables that are associated with hdlc baseline ( p<0.05 ) was also constructed . to determine the interaction between hdlc and ldlc
, a stratified regression analysis was performed using specific ldlc cutoff points ( < 70 , 70 to 100 , and 100 mg / dl ) .
the interaction between hdlc and ldlc was also determined by including an interaction term in the model .
if the p value of the interaction term was < 0.05 , effect modification was considered to be present .
multiple testing was corrected using false discovery rate ( fdr ) q values calculated by the benjaminihochberg method . to date
, there is no conventional qvalue threshold to categorize a discovery as significant . as in previous studies , a qvalue threshold of 0.20
between december 2010 and december 2012 , 2646 consecutive patients with normal levels of cardiac troponin i ( ctni ) and creatine kinasemb ( ckmb ) and without acute myocardial infarction in the past 4 weeks who attempted to undergo elective pci at our center were eligible for this study . of these patients , 96 patients were excluded because a total chronic occlusion could not be crossed with a wire ; 2 patients were excluded because a subtotal chronic occlusion could not be crossed with a wire ; 4 patients were excluded because a severely calcified or tortuous lesion could not be crossed with a balloon ; 10 patients were excluded because they were treated with atheroablative , distal protection devices , or aspiration thrombectomy ; and 5 patients were excluded because of residual stenosis more than 50% with angioplasty only .
angiographic success of pci was defined as residual stenosis < 20% with stenting and residual stenosis
unstable angina was defined as rest angina , newonset severe angina , and increasing angina within 2 months .
secondly , postprocedural ctni > 3uln , which was the diagnosis criteria of periprocedural myocardial infarction published in 2007 , and postprocedural ctni > 5uln , which was a requirement in the arbitrarily revised diagnosis criteria published in 2012 , were also examined in this study .
this study was approved by the ethics committee of fuwai hospital , complied with the declaration of helsinki , and all patients gave their informed consent for participation in this study .
the indication for pci was based on the american college of cardiology / american heart association recommendations and was performed by experienced interventional cardiologists . before the procedure
, all patients without contraindications received aspirin 100 mg daily or a loading dose of 300 mg , depending on whether daily aspirin therapy was already taken , and received clopidogrel 75 mg daily or a loading dose of 300 mg , depending on whether daily longterm clopidogrel therapy was already taken prior to intervention .
all patients received either 5000 u or 70 u / kg bolus of unfractionated heparin just before the procedure , and an additional bolus of 2000 to 3000 u was given every hour if the procedure lasted for > 1 hour .
vascular access and pci type ( angioplasty only , angioplasty and stenting , or primary stenting ) were determined by the interventional cardiologist according to the patient characteristics .
total balloon inflation times and inflation pressures were determined by the interventional cardiologist according to the technical properties of the balloon and the stent . after the procedure , all patients continued with aspirin and clopidogrel therapy daily .
use of glycoprotein iib / iiia receptor antagonists or anticoagulants was at the discretion of the interventional cardiologist .
in all patients , a 12lead ecg was recorded before , immediately after pci , and in the case of the occurrence of symptoms that were interpreted as a postprocedural ischemic event .
the hdlc concentration was determined by a homogeneous method ( determiner l hdl , kyowa medex , tokyo ) with a coefficient of variation of < 5% and a total imprecision of < 10% .
the ldlc concentration was analyzed by selective solubilization method ( ldlc test kit , kyowa medex , tokyo ) with a coefficient of variation of < 5% and a total imprecision of < 10% .
ctni levels were determined in venous blood samples before pci , 24 hours after pci , and in the event of the occurrence of symptoms or signs suggestive of myocardial ischemia .
ctni was analyzed by an immunochemiluminometric assay ( access accutni , beckman coulter , ca ) .
the uln was defined as the 99th percentile of normal population with a total imprecision of < 10% .
the uln of this test was 0.04 ng / ml . the ckmb activity was determined before pci by an immunoinhibition assay ( creatine kinasemb kit , biosino , beijing ) with a uln of 24 u / l .
data are presented as meansd , median with interquartile ranges , or frequencies with percentages , as appropriate .
comparisons among groups were made with analysis of variance ,  test , fisher 's exact test , or kruskal  wallis test as appropriate .
univariate linear regression analyses were performed to determine the association between clinical parameters and postprocedural ctni levels .
variables with a p value < 0.1 in the univariate linear regression were entered into a stepwise multivariable linear model to determine the independent association between clinical parameters and postprocedural ctni levels .
logistic regression analyses were performed to determine the relationship of hdlc with the occurrence of postprocedural ctni elevations above various multiples of uln .
additionally , a separate model adjusting for variables that are associated with hdlc baseline ( p<0.05 ) was also constructed . to determine the interaction between hdlc and ldlc
, a stratified regression analysis was performed using specific ldlc cutoff points ( < 70 , 70 to 100 , and 100 mg / dl ) .
the interaction between hdlc and ldlc was also determined by including an interaction term in the model .
if the p value of the interaction term was < 0.05 , effect modification was considered to be present
multiple testing was corrected using false discovery rate ( fdr ) q values calculated by the benjaminihochberg method . to date , there is no conventional qvalue threshold to categorize a discovery as significant .
as in previous studies , a qvalue threshold of 0.20 was used to define significance .
the hdlc ranged from 18.6 to 109.8 mg / dl ( median 39.8 mg / dl , interquartile range 34.4 to 47.1 mg / dl , mean 41.610.3 mg / dl ) ( figure 1 ) .
the baseline clinical characteristics of the subjects in each of the quartiles of hdlc level are shown in table 1 .
subjects with lower hdlc levels were younger , more likely to be male and current smokers , and had higher body mass index than those with higher hdlc levels . diabetes mellitus and a history of myocardial infarction were more common in the lower quartiles of hdlc levels .
subjects with lower hdlc levels had higher highsensitivity creactive protein , triglyceride , and glycated hemoglobin .
baseline clinical characteristics values are expressed as meansd , median with interquartile range or n ( % ) .
ace indicates angiotensinconverting enzyme ; arbs , angiotensin receptor blockers ; bmi , body mass index ; cabg , coronary artery bypass graft ; ccbs , calcium channel blockers ; ctni , cardiac troponin family history i ; fh , ; hba1c , glycosylated hemoglobin ; hdlc , highdensity lipoprotein cholesterol ; hscrp , highsensitivity creactive protein ; ldlc , lowdensity lipoprotein cholesterol ; mi , myocardial infarction ; ntprobnp , nterminal probrain natriuretic peptide ; pci , percutaneous coronary intervention ; ua , unstable angina .
the procedural characteristics of the subjects within quartiles of hdlc are shown in table 2 .
subjects with higher hdlc levels were likely to receive fewer stents and shorter total stent length implanted with less predilation times .
there were no significant differences in vascular access , target vessel , target lesion site , and target lesion type among groups .
there were also no significant differences in maximum inflation pressure , maximum inflation time , and postdilation times among quartiles of hdlc .
procedural characteristics values are expressed as n ( % ) , meansd , or median with interquartile range .
acc / aha indicates american college of cardiology / american heart association ; gpi , glycoprotein inhibitor ; hdlc , highdensity lipoprotein cholesterol ; lad , left anterior descending ; lcx , left circumflex ; lima , left internal mammary artery ; lm , left main ; lmwh , lowmolecularweight heparin ; rca , right coronary artery ; svg , saphenous vein graft .
peak postprocedural ctni > 1uln , > 3uln , and > 5uln were detected in 1455 ( 57.5% ) , 866 ( 34.2% ) , and 646 ( 25.5% ) , respectively .
stepwise multivariable analysis demonstrated that factors independently associated with postprocedural ctni ( logtransformed ) were age , prior myocardial infarction , unstable angina , family history of coronary artery disease ( cad ) , ldlc , nterminal probrain natriuretic peptide , preprocedural ctni , hemoglobin , glycated hemoglobin , number of target vessels , number of type b2/c lesions , number of bifurcation lesions , number of postdilation , and number of stents .
the risk of postprocedural ctni elevation was determined for each quintile of hdlc level across the entire cohort .
the quintiles of hdlc showed no significant association with postprocedural ctni elevation above 1uln , 3uln , and 5uln .
there was also no significant association after adjusting for variables that were independently associated with postprocedural ctni levels ( table 3 ) .
odds ratio ( or ) for postprocedural ctni elevation according to quintiles of hdlc adjusted model included age , prior myocardial infarction , family history of cad , ldlc , ntprobnp , preprocedural ctni , number of target vessels , number of type b2/c lesions , number of bifurcation lesions , number of postdilation , number of stents , unstable angina , hemoglobin , and glycated hemoglobin .
cad indicates coronary artery disease ; ctni , cardiac troponin i ; hdlc , highdensity lipoprotein cholesterol ; ldlc , lowdensity lipoprotein cholesterol ; ntprobnp , nterminal probrain natriuretic peptide ; or , odds ratio ; pci , percutaneous coronary intervention ; uln , upper limit of normal . calculating hdlc as a continuous variable , each increment of 1 mg / dl in the hdlc level was not significantly associated with postprocedural ctni elevation above 1uln , 3uln , and 5uln .
there was also no significant association after adjusting for variables that were independently associated with postprocedural ctni levels ( table 4 ) .
additionally , after adjusting for variables that were clearly different among hdlc quintiles , there was also no significant association of hdlc levels or quintiles with postprocedural ctni elevation above 1uln , 3uln , and 5uln ( tables 5 and 6 ) .
odds ratio ( or ) for postprocedural ctni elevation associated with 1 mg / dl increment in hdlc adjusted model included age , prior myocardial infarction , family history of cad , ldlc , ntprobnp , preprocedural ctni , number of target vessels , number of type b2/c lesions , number of bifurcation lesions , number of postdilation , number of stents , unstable angina , hemoglobin and glycated hemoglobin .
cad indicates coronary artery disease ; ctni , cardiac troponin i ; hdlc , highdensity lipoprotein cholesterol ; ldlc , lowdensity lipoprotein cholesterol ; ntprobnp , nterminal probrain natriuretic peptide ; pci , percutaneous coronary intervention ; uln , upper limit of normal .
odds ratio ( or ) for postprocedural ctni elevation according to quintiles of hdlc adjusted model included age , sex , bmi , diabetes , current smoking , prior myocardial infarction , prior pci , ldlc , triglyceride , hscrp , ntprobnp , hba1c , hemoglobin , occlusion lesions , number of stents implanted , total stent length , and number of predilations .
bmi indicates body mass index ; ctni , cardiac troponin i ; hba1c , glycosylated hemoglobin ; hdlc , highdensity lipoprotein cholesterol ; hscrp , highsensitivity creactive protein ; ldlc , lowdensity lipoprotein cholesterol ; ntprobnp , nterminal probrain natriuretic peptide ; pci , percutaneous coronary intervention ; uln , upper limit of normal .
odds ratio ( or ) for postprocedural ctni elevation associated with 1 mg / dl increment in hdlc adjusted model included age , sex , bmi , diabetes , current smoking , prior myocardial infarction , prior pci , ldlc , triglyceride , hscrp , ntprobnp , hba1c , hemoglobin , occlusion lesions , number of stents implanted , total stent length , and number of predilations .
bmi indicates body mass index ; ctni , cardiac troponin i ; hba1c , glycosylated hemoglobin ; hdlc , highdensity lipoprotein cholesterol ; hscrp , highsensitivity creactive protein ; ldlc , lowdensity lipoprotein cholesterol ; ntprobnp , nterminal probrain natriuretic peptide ; pci , percutaneous coronary intervention ; uln , upper limit of normal .
we performed a stratified regression analysis using prespecified ldlc categories ( < 70 mg / dl , n=559 ; 70 to 100 mg / dl , n=965 ; and 100 mg / dl , n=1005 ) .
patients with ldlc < 70 mg / dl were more likely to be men ( 66.2% , 64.0% versus 53.7% , p<0.001 ) , and less likely to be current smokers ( 25.4% , 32.4% versus 32.5% , p=0.006 ) . patients with ldlc < 70 mg / dl had a lower hdlc level ( 39.0 , 40.9 versus 43.6 mg / dl , p<0.001 ) , triglyceride ( 108 , 130 versus 146 mg / dl , p<0.001 ) , and highsensitivity creactive protein ( 1.37 , 1.48 versus 1.88 mg / dl , p<0.001 ) .
there were no significant differences in age , body mass index , diabetes , hypertension , and family history of cad among the 3 groups ( all p>0.05 ) .
figures 2 through 4 show the stratified regression analysis results using specific ldlc cutoff points . in patients with ldlc < 70 mg / dl , compared with the first quintile of hdlc ,
the fifth quintile was associated with less risk of postprocedural ctni elevation above 1uln ( or : 0.35 ; 95% ci : 0.18 to 0.66 ; p=0.001 ; fdr q=0.009 ) , 3uln ( odds ratio : 0.45 ; 95% ci : 0.23 to 0.90 ; p=0.023 ; fdr q=0.075 ) and 5uln ( odds ratio : 0.42 ; 95% ci : 0.19 to 0.90 ; p=0.025 ; fdr q=0.075 ) .
however , there was no significant association between hdlc quintiles and the risk of postprocedural ctni elevation in patients with ldlc 70 to 100 mg / dl and in patients with ldlc 100 mg / dl . calculating hdlc as a continuous variable , each increment of 1 mg / dl in the hdlc level
was also associated with less risk of postprocedural ctni elevation above 1uln , 3uln , and 5uln only in patients with ldlc < 70 mg / dl ( table 7 , all p values < 0.05 and all fdr q values < 0.20 ) , and not associated in patients with ldlc 70 to 100 mg / dl and in patients with ldlc 100 mg / dl ( table 7 , all p values > 0.05 and all fdr q values > 0.20 ) .
additionally , after adjusting for variables that are clearly different among hdlc quintiles , the results were similar ( table 8) .
the relation between plasma hdlc level and risk of postprocedural ctni elevation above 1uln , 3uln , and 5uln was modified by ldlc level ( p for interaction = 0.008 , 0.005 , 0.012 , respectively ) .
odds ratio ( or ) for postprocedural ctni elevation associated with 1 mg / dl increment in the hdlc stratified by ldlc level adjusted model included age , prior myocardial infarction , family history of cad , ldlc , ntprobnp , preprocedural ctni , number of target vessels , number of type b2/c lesions , number of bifurcation lesions , number of postdilation , number of stents , unstable angina , hemoglobin , and glycated hemoglobin .
cad indicates coronary artery disease ; ctni , cardiac troponin i ; hdlc , highdensity lipoprotein cholesterol ; ldlc , lowdensity lipoprotein cholesterol ; ntprobnp , nterminal probrain natriuretic peptide ; pci , percutaneous coronary intervention ; uln , upper limit of normal .
odds ratio ( or ) for postprocedural ctni elevation associated with 1 mg / dl increment in the hdlc stratified by ldlc level adjusted model included age , sex , bmi , diabetes , current smoking , prior myocardial infarction , prior pci , ldlc , triglyceride , hscrp , ntprobnp , hba1c , hemoglobin , occlusion lesions , number of stents implanted , total stent length , and number of predilations .
bmi indicates body mass index ; ctni , cardiac troponin i ; hba1c , glycosylated hemoglobin ; hdlc , highdensity lipoprotein cholesterol ; hscrp , highsensitivity creactive protein ; ldlc , lowdensity lipoprotein cholesterol ; ntprobnp , nterminal probrain natriuretic peptide ; pci , percutaneous coronary intervention ; uln , upper limit of normal .
association of hdlc quintile with the risk of postprocedural ctni > 1uln by ldlc subgroup .
odds ratios were adjusted for age , prior myocardial infarction , family history of cad , ldlc , ntprobnp , preprocedural ctni , number of target vessels , number of type b2/c lesions , number of bifurcation lesions , number of postdilation , number of stents , unstable angina , hemoglobin , and glycated hemoglobin .
cad indicates coronary artery disease ; ctni , cardiac troponin i ; hdlc , highdensity lipoprotein cholesterol ; ldlc , lowdensity lipoprotein cholesterol ; ntprobnp , nterminal probrain natriuretic peptide ; uln , upper limit of normal .
association of hdlc quintile with the risk of postprocedural ctni > 3uln by ldlc subgroup .
odds ratios were adjusted for age , prior myocardial infarction , family history of cad , ldlc , ntprobnp , preprocedural ctni , number of target vessels , number of type b2/c lesions , number of bifurcation lesions , number of postdilation , number of stents , unstable angina , hemoglobin , and glycated hemoglobin .
cad indicates coronary artery disease ; ctni , cardiac troponin i ; hdlc , highdensity lipoprotein cholesterol ; ldlc , lowdensity lipoprotein cholesterol ; ntprobnp , nterminal probrain natriuretic peptide ; uln , upper limit of normal .
association of hdlc quintile with the risk of postprocedural ctni > 5uln by ldlc subgroup .
odds ratios were adjusted for age , prior myocardial infarction , family history of cad , ldlc , ntprobnp , preprocedural ctni , number of target vessels , number of type b2/c lesions , number of bifurcation lesions , number of postdilation , number of stents , unstable angina , hemoglobin and glycated hemoglobin .
cad indicates coronary artery disease ; ctni , cardiac troponin i ; hdlc , highdensity lipoprotein cholesterol ; ldlc , lowdensity lipoprotein cholesterol ; ntprobnp , nterminal probrain natriuretic peptide ; uln , upper limit of normal .
the hdlc ranged from 18.6 to 109.8 mg / dl ( median 39.8 mg / dl , interquartile range 34.4 to 47.1 mg / dl , mean 41.610.3 mg / dl ) ( figure 1 ) .
the baseline clinical characteristics of the subjects in each of the quartiles of hdlc level are shown in table 1 .
subjects with lower hdlc levels were younger , more likely to be male and current smokers , and had higher body mass index than those with higher hdlc levels . diabetes mellitus and a history of myocardial infarction were more common in the lower quartiles of hdlc levels .
subjects with lower hdlc levels had higher highsensitivity creactive protein , triglyceride , and glycated hemoglobin .
baseline clinical characteristics values are expressed as meansd , median with interquartile range or n ( % ) .
ace indicates angiotensinconverting enzyme ; arbs , angiotensin receptor blockers ; bmi , body mass index ; cabg , coronary artery bypass graft ; ccbs , calcium channel blockers ; ctni , cardiac troponin family history i ; fh , ; hba1c , glycosylated hemoglobin ; hdlc , highdensity lipoprotein cholesterol ; hscrp , highsensitivity creactive protein ; ldlc , lowdensity lipoprotein cholesterol ; mi , myocardial infarction ; ntprobnp , nterminal probrain natriuretic peptide ; pci , percutaneous coronary intervention ; ua , unstable angina .
the procedural characteristics of the subjects within quartiles of hdlc are shown in table 2 .
subjects with higher hdlc levels were likely to receive fewer stents and shorter total stent length implanted with less predilation times .
there were no significant differences in vascular access , target vessel , target lesion site , and target lesion type among groups .
there were also no significant differences in maximum inflation pressure , maximum inflation time , and postdilation times among quartiles of hdlc .
procedural characteristics values are expressed as n ( % ) , meansd , or median with interquartile range .
acc / aha indicates american college of cardiology / american heart association ; gpi , glycoprotein inhibitor ; hdlc , highdensity lipoprotein cholesterol ; lad , left anterior descending ; lcx , left circumflex ; lima , left internal mammary artery ; lm , left main ; lmwh , lowmolecularweight heparin ; rca , right coronary artery ; svg , saphenous vein graft .
peak postprocedural ctni > 1uln , > 3uln , and > 5uln were detected in 1455 ( 57.5% ) , 866 ( 34.2% ) , and 646 ( 25.5% ) , respectively .
stepwise multivariable analysis demonstrated that factors independently associated with postprocedural ctni ( logtransformed ) were age , prior myocardial infarction , unstable angina , family history of coronary artery disease ( cad ) , ldlc , nterminal probrain natriuretic peptide , preprocedural ctni , hemoglobin , glycated hemoglobin , number of target vessels , number of type b2/c lesions , number of bifurcation lesions , number of postdilation , and number of stents .
the risk of postprocedural ctni elevation was determined for each quintile of hdlc level across the entire cohort .
the quintiles of hdlc showed no significant association with postprocedural ctni elevation above 1uln , 3uln , and 5uln .
there was also no significant association after adjusting for variables that were independently associated with postprocedural ctni levels ( table 3 ) .
odds ratio ( or ) for postprocedural ctni elevation according to quintiles of hdlc adjusted model included age , prior myocardial infarction , family history of cad , ldlc , ntprobnp , preprocedural ctni , number of target vessels , number of type b2/c lesions , number of bifurcation lesions , number of postdilation , number of stents , unstable angina , hemoglobin , and glycated hemoglobin .
cad indicates coronary artery disease ; ctni , cardiac troponin i ; hdlc , highdensity lipoprotein cholesterol ; ldlc , lowdensity lipoprotein cholesterol ; ntprobnp , nterminal probrain natriuretic peptide ; or , odds ratio ; pci , percutaneous coronary intervention ; uln , upper limit of normal . calculating hdlc as a continuous variable , each increment of 1 mg / dl in the hdlc level was not significantly associated with postprocedural ctni elevation above 1uln , 3uln , and 5uln .
there was also no significant association after adjusting for variables that were independently associated with postprocedural ctni levels ( table 4 ) .
additionally , after adjusting for variables that were clearly different among hdlc quintiles , there was also no significant association of hdlc levels or quintiles with postprocedural ctni elevation above 1uln , 3uln , and 5uln ( tables 5 and 6 ) .
odds ratio ( or ) for postprocedural ctni elevation associated with 1 mg / dl increment in hdlc adjusted model included age , prior myocardial infarction , family history of cad , ldlc , ntprobnp , preprocedural ctni , number of target vessels , number of type b2/c lesions , number of bifurcation lesions , number of postdilation , number of stents , unstable angina , hemoglobin and glycated hemoglobin .
cad indicates coronary artery disease ; ctni , cardiac troponin i ; hdlc , highdensity lipoprotein cholesterol ; ldlc , lowdensity lipoprotein cholesterol ; ntprobnp , nterminal probrain natriuretic peptide ; pci , percutaneous coronary intervention ; uln , upper limit of normal .
odds ratio ( or ) for postprocedural ctni elevation according to quintiles of hdlc adjusted model included age , sex , bmi , diabetes , current smoking , prior myocardial infarction , prior pci , ldlc , triglyceride , hscrp , ntprobnp , hba1c , hemoglobin , occlusion lesions , number of stents implanted , total stent length , and number of predilations .
bmi indicates body mass index ; ctni , cardiac troponin i ; hba1c , glycosylated hemoglobin ; hdlc , highdensity lipoprotein cholesterol ; hscrp , highsensitivity creactive protein ; ldlc , lowdensity lipoprotein cholesterol ; ntprobnp , nterminal probrain natriuretic peptide ; pci , percutaneous coronary intervention ; uln , upper limit of normal .
odds ratio ( or ) for postprocedural ctni elevation associated with 1 mg / dl increment in hdlc adjusted model included age , sex , bmi , diabetes , current smoking , prior myocardial infarction , prior pci , ldlc , triglyceride , hscrp , ntprobnp , hba1c , hemoglobin , occlusion lesions , number of stents implanted , total stent length , and number of predilations .
bmi indicates body mass index ; ctni , cardiac troponin i ; hba1c , glycosylated hemoglobin ; hdlc , highdensity lipoprotein cholesterol ; hscrp , highsensitivity creactive protein ; ldlc , lowdensity lipoprotein cholesterol ; ntprobnp , nterminal probrain natriuretic peptide ; pci , percutaneous coronary intervention ; uln , upper limit of normal .
we performed a stratified regression analysis using prespecified ldlc categories ( < 70 mg / dl , n=559 ; 70 to 100 mg / dl , n=965 ; and 100 mg / dl , n=1005 ) .
patients with ldlc < 70 mg / dl were more likely to be men ( 66.2% , 64.0% versus 53.7% , p<0.001 ) , and less likely to be current smokers ( 25.4% , 32.4% versus 32.5% , p=0.006 ) . patients with ldlc
< 70 mg / dl had a lower hdlc level ( 39.0 , 40.9 versus 43.6 mg / dl , p<0.001 ) , triglyceride ( 108 , 130 versus 146 mg / dl , p<0.001 ) , and highsensitivity creactive protein ( 1.37 , 1.48 versus 1.88 mg / dl , p<0.001 ) . there were no significant differences in age , body mass index , diabetes , hypertension , and family history of cad among the 3 groups ( all p>0.05 ) .
figures 2 through 4 show the stratified regression analysis results using specific ldlc cutoff points . in patients with ldlc < 70 mg / dl , compared with the first quintile of hdlc
, the fifth quintile was associated with less risk of postprocedural ctni elevation above 1uln ( or : 0.35 ; 95% ci : 0.18 to 0.66 ; p=0.001 ; fdr q=0.009 ) , 3uln ( odds ratio : 0.45 ; 95% ci : 0.23 to 0.90 ; p=0.023 ; fdr q=0.075 ) and 5uln ( odds ratio : 0.42 ; 95% ci : 0.19 to 0.90 ; p=0.025 ; fdr q=0.075 ) .
however , there was no significant association between hdlc quintiles and the risk of postprocedural ctni elevation in patients with ldlc 70 to 100 mg / dl and in patients with ldlc 100 mg / dl .
calculating hdlc as a continuous variable , each increment of 1 mg / dl in the hdlc level was also associated with less risk of postprocedural ctni elevation above 1uln , 3uln , and 5uln only in patients with ldlc < 70 mg / dl ( table 7 , all p values < 0.05 and all fdr q values < 0.20 ) , and not associated in patients with ldlc 70 to 100 mg / dl and in patients with ldlc 100 mg / dl ( table 7 , all p values > 0.05 and all fdr q values > 0.20 ) .
additionally , after adjusting for variables that are clearly different among hdlc quintiles , the results were similar ( table 8) . the relation between plasma hdlc level and risk of postprocedural ctni elevation above 1uln , 3uln , and 5uln was modified by ldlc level ( p for interaction = 0.008 , 0.005 , 0.012 , respectively ) .
odds ratio ( or ) for postprocedural ctni elevation associated with 1 mg / dl increment in the hdlc stratified by ldlc level adjusted model included age , prior myocardial infarction , family history of cad , ldlc , ntprobnp , preprocedural ctni , number of target vessels , number of type b2/c lesions , number of bifurcation lesions , number of postdilation , number of stents , unstable angina , hemoglobin , and glycated hemoglobin .
cad indicates coronary artery disease ; ctni , cardiac troponin i ; hdlc , highdensity lipoprotein cholesterol ; ldlc , lowdensity lipoprotein cholesterol ; ntprobnp , nterminal probrain natriuretic peptide ; pci , percutaneous coronary intervention ; uln , upper limit of normal .
odds ratio ( or ) for postprocedural ctni elevation associated with 1 mg / dl increment in the hdlc stratified by ldlc level adjusted model included age , sex , bmi , diabetes , current smoking , prior myocardial infarction , prior pci , ldlc , triglyceride , hscrp , ntprobnp , hba1c , hemoglobin , occlusion lesions , number of stents implanted , total stent length , and number of predilations .
bmi indicates body mass index ; ctni , cardiac troponin i ; hba1c , glycosylated hemoglobin ; hdlc , highdensity lipoprotein cholesterol ; hscrp , highsensitivity creactive protein ; ldlc , lowdensity lipoprotein cholesterol ; ntprobnp , nterminal probrain natriuretic peptide ; pci , percutaneous coronary intervention ; uln , upper limit of normal .
association of hdlc quintile with the risk of postprocedural ctni > 1uln by ldlc subgroup .
odds ratios were adjusted for age , prior myocardial infarction , family history of cad , ldlc , ntprobnp , preprocedural ctni , number of target vessels , number of type b2/c lesions , number of bifurcation lesions , number of postdilation , number of stents , unstable angina , hemoglobin , and glycated hemoglobin .
cad indicates coronary artery disease ; ctni , cardiac troponin i ; hdlc , highdensity lipoprotein cholesterol ; ldlc , lowdensity lipoprotein cholesterol ; ntprobnp , nterminal probrain natriuretic peptide ; uln , upper limit of normal .
association of hdlc quintile with the risk of postprocedural ctni > 3uln by ldlc subgroup .
odds ratios were adjusted for age , prior myocardial infarction , family history of cad , ldlc , ntprobnp , preprocedural ctni , number of target vessels , number of type b2/c lesions , number of bifurcation lesions , number of postdilation , number of stents , unstable angina , hemoglobin , and glycated hemoglobin .
cad indicates coronary artery disease ; ctni , cardiac troponin i ; hdlc , highdensity lipoprotein cholesterol ; ldlc , lowdensity lipoprotein cholesterol ; ntprobnp , nterminal probrain natriuretic peptide ; uln , upper limit of normal .
association of hdlc quintile with the risk of postprocedural ctni > 5uln by ldlc subgroup .
odds ratios were adjusted for age , prior myocardial infarction , family history of cad , ldlc , ntprobnp , preprocedural ctni , number of target vessels , number of type b2/c lesions , number of bifurcation lesions , number of postdilation , number of stents , unstable angina , hemoglobin and glycated hemoglobin .
cad indicates coronary artery disease ; ctni , cardiac troponin i ; hdlc , highdensity lipoprotein cholesterol ; ldlc , lowdensity lipoprotein cholesterol ; ntprobnp , nterminal probrain natriuretic peptide ; uln , upper limit of normal .
the present study demonstrates that low hdlc was associated with an increased risk of periprocedural myocardial injury only in patients with ldlc < 70 mg / dl , but not in patients with ldlc 70 to 100 mg / dl and in patients with ldlc 100 mg / dl .
gordon et al found a consistent inverse relation of hdlc levels with cad event rates by using the same analytic approach in 4 prospective studies , and 1 mg / dl increment in hdlc levels was associated with decreased risk of cad by 2% to 3% .
however , a low level of hdlc does not necessarily mean increased risk of cardiovascular events or mortality . decreased hdlc levels due to rare and common genetic variants were both not associated with increased risk of cardiovascular diseases .
a strong inverse association between hdlc and cardiovascular risk has led to intensive research seeking to raise plasma levels of hdlc . however , several studies have not shown reduced cardiovascular risk with therapeutic agents that raised hdlc significantly such as niacin , fibrates , and cholesteryl ester transfer protein inhibitors .
the results of these trials have challenged this concept that hdlc was inversely associated with cardiovascular risk . moreover , higher hdlc even changed into a significant major cardiac event risk factor following adjustment for apoai and apob . whether low hdlc is a cause or is merely a biomarker of cardiovascular disease remains controversial .
it has been suggested that hdl protects against atherosclerosis through reverse cholesterol transport and antiinflammatory and antioxidant properties .
hdlc levels were a poor surrogate for cholesterol efflux capacity of hdl , which plays a key role in reverse cholesterol transport .
though experimental observations showed these atheroprotective functions of hdl isolated from healthy subjects , hdl isolated from patients with cad was shown to lose these properties .
hdl has been shown to undergo a loss of functions in several pathophysiological states , such as smoking , diabetes mellitus , dyslipidemia , and inflammation .
khera et al demonstrated that cholesterol efflux capacity of hdl was a stronger and independent inverse predictor of cad than hdlc levels , supporting the argument that measures of hdl function may be more useful than hdlc levels in cardiovascular risk prediction.silbernagel and colleagues investigated the relation of hdlc with cardiovascular mortality in 3141 participants with or without cad , and found that hdlc was inversely associated with cardiovascular mortality in people without cad , but not in patients with cad .
a recent study demonstrated that higher hdlc levels were not associated with a reduced risk of vascular events in 1548 patients with cad undergoing elective bypass surgery with a median followup time of 32 months .
our study demonstrated that hdlc was not associated with the risk of periprocedural myocardial injury in the entire cohort .
there were multiple studies assessing the associations of hdlc with cardiovascular risk across the range of ldlc levels .
as early as 1991 , a prospective study has demonstrated that the benefit of a higher hdl cholesterol level was most pronounced among those with lower total cholesterol levels . in a combined analysis of 2 secondary prevention trials with pravastatin that included 13 173 participants with cad ,
hdlc was a significantly stronger predictor of recurrent cad events in participants with ldlc < 125 than in those with 125 mg / dl during a 5.8year followup . in a posthoc analysis of 2193 patients with stable cad from the clinical outcomes utilizing revascularization and aggressive drug evaluation ( courage ) trial , the inverse association of hdlc with cardiovascular risk was the most prominent in patients with ldlc levels < 70 mg / dl . among 2661 participants with ldlc levels
< 70 mg / dl in the treating to new targets ( tnt ) trial , higher hdlc levels were associated with less risk of major cardiovascular events .
the present study demonstrates that higher hdlc was associated with less risk of periprocedural myocardial injury only in patients with ldlc < 70 mg / dl .
our study complements the evidence already given for the greater predictive value of hdlc for cardiovascular risk in patients with low ldlc .
these studies may suggest that hdlc levels correlated more with hdl functions in patients with low ldlc levels . in our study , patients with ldlc levels 70 mg / dl have levels of higher triglyceride and creactive protein , which might lead to dysfunction of hdl .
in contrast to our data , sattler et al found that small increases in hdlc in patients undergoing elective pci converted into a substantial reduction of risk for pcirelated myocardial infarction in the entire cohort .
another possible explanation is that hdlc levels correlate well with hdl function in the study population .
however , there was an inconsistent pattern when comparing the associations of hdlc with cardiovascular risk among patients with different intensities of statin therapy .
in the justification for the use of statins in primary prevention : an intervention trial evaluating rosuvastatin ( jupiter ) trial , the inverse association between hdlc and vascular events was not observed in patients on rosuvastatin 20 mg / day , whereas it did exist in patients on placebo .
the treating to new targets ( tnt ) trial showed that the association of hdlc with cardiovascular risk was markedly attenuated in patients randomized to atorvastatin 80 mg / day .
similarly , the pravastatin or atorvastatin evaluation and infection therapythrombolysis in myocardial infarction 22 ( prove ittimi 22 ) trial found no predictive value for hdlc in patients on atorvastatin 80 mg / day . in a metaanalysis of 8 statin trials ,
hdlc increase during statin therapy was not associated with a reduced risk of major cardiovascular events .
the hdlcincreasing effect of statins is caused by inhibition of cholesteryl ester transfer protein activity , and is unrelated to changes in ldlc by statins . whether the loss of relation of hdlc and cardiovascular risk in intensive statin therapy can be explained by functional changes in hdl during intensive statin therapy , or whether reverse cholesterol transport , antiinflammatory , and antioxidant properties of hdlc are less relevant than highdose statin therapy is unclear .
whether hdl alteration during statin therapy contributes to considerable residual risk in primary and secondary prevention trials with statins is unknown . instead of just focusing on the dose , type , and duration of statin treatment , we used the target levels of ldlc lowering recommended by the national cholesterol education program adult treatment panel iii guidelines , an ideal approach that was close to clinical practice .
the inconsistent results about the relation of hdlc with cardiovascular risk between patients with < 70 mg / dl and those with intense statin therapy might suggest that intense statin therapy was not identical to achieving an ldlc level < 70 mg / dl .
it might also suggest that achieving an ldlc level < 70 mg / dl recommended by guidelines was more important than intensive statin therapy .
regardless , those with higher levels of hdlc experienced reduced risk of periprocedural myocardial injury when ldlc was reduced to < 70 mg / dl in patients undergoing elective pci . despite the detailed data collection and the large number of patients in this study , several limitations of this study should be noted .
first , although we attempted to adjust for potential confounders , we can not exclude the possibility that unmeasured variables may have confounded results .
the subgroup analysis might be a result from the small number of patients in some groups .
third , it has been suggested that ckmb might have a better predictive value than troponins , but we did not measure the ckmb levels after the procedure .
however , troponins are more sensitive and specific biomarkers for myocardium than ckmb , and the third universal definition of myocardial infarction has recommended use of troponin for diagnosis of pcirelated myocardial infarction and injury .
thus , we just measured the ckmb activity before the procedure and did not measure the ckmb mass after the procedure due to insurance cost .
fourth , some recent studies have shown that hdlc may not be cardioprotective mediators , which may diminish the significance in this subgroup analysis .
fifth , although we applied the fdr method to correct for multiple testing and used a threshold of q<0.2 to determine statistical significance as in previous studies , we can not exclude the possibilities of reporting false positives through performing many hypothesis tests .
the present study showed that only higher hdlc levels were associated with reduced risk of periprocedural myocardial injury in patients with ldlc < 70 mg / dl .
our findings suggested that hdlc might be a potential therapeutic target only when ldlc is reduced to optimal levels .
the authors thank the staff of the cardiac catheterization laboratory at fu wai hospital for their assistance in performing the studies .
 backgroundrecent data showed inconsistent association of highdensity lipoprotein cholesterol ( hdlc ) with cardiovascular risk in patients with different levels of lowdensity lipoprotein cholesterol ( ldlc ) or intensive statin therapy . 
 this study sought to determine the relationship of hdlc with periprocedural myocardial injury following elective percutaneous coronary intervention ( pci ) across a range of ldlc levels , especially in patients with ldlc < 70 mg / dl.methods and resultswe enrolled 2529 consecutive patients with normal preprocedural cardiac troponin i ( ctni ) who underwent elective pci . 
 the association between preprocedural hdlc and periprocedural myocardial injury was evaluated across ldlc levels , especially in patients with ldlc < 70 mg / dl . 
 the hdlc level was not predictive of periprocedural myocardial injury across the entire study cohort . 
 however , among patients with ldlc < 70 mg / dl , a 1 mg / dl increase in hdlc was associated with a 3% reduced risk for postprocedural ctni above 1upper limit of normal ( uln ) ( odds ratio : 0.97 ; 95% ci : 0.95 to 0.99 ; p=0.004 ) , a 3% reduced risk for postprocedural ctni above 3uln odds ratio : 0.97 ; 95% ci : 0.95 to 0.99 ; p=0.022 ) , and a 3% reduced risk for postprocedural ctni above 5uln ( odds ratio : 0.97 ; 95% ci : 0.95 to 0.99 ; p=0.017 ) . 
 the relation between plasma hdlc level and risk of postprocedural ctni elevation above 1uln , 3uln , and 5uln was modified by ldlc level ( all p for interaction < 0.05).conclusionshigher hdlc levels were associated with reduced risk of periprocedural myocardial injury only in patients with ldlc < 70 mg / dl . 
Introduction
Methods
Patient Population
Percutaneous Coronary Artery Intervention
ECG Monitoring
Lipid Profile and Plasma Markers
Statistics
Results
Baseline Characteristics
Factors Independently Associated With Postprocedural cTnI Level
HDLC and Risk of Postprocedural cTnI Elevation
Association of HDLC With the Risk of Postprocedural cTnI Elevation by LDLC Subgroup
Discussion
Conclusions
Acknowledgments