dyslipidemias , especially characterized by high serum level of low density lipoprotein - cholesterol ( ldl - c ) , has been well documented as an important risk factor of atherosclerosis and its manifestation of atherosclerotic cardiovascular diseases ( cvd ) . in the past decades , accumulating evidence from clinical studies firmly demonstrates that ldl - c decreased by lipid - lowering drug , such as hmg - coa reductase inhibitor ( statins ) , is crucial for reducing the incidence of coronary heart diseases ( chd ) , ischemic stroke , and peripheral artery diseases [ 25 ] . however , some epidemiological studies show that , although target ldl - c level has been achieved by statins therapy , residual cardiovascular risk such as restenosis after stent placement in some population groups is still very high [ 68 ] , suggesting that , besides ldl - c , other risk factors could also play a contributory role in the progression and recurrence of cvd , and identifying those potential risk factors would be useful , helpful , and beneficial for further improving cardiovascular outcome . lipoprotein(a ) ( lp(a ) ) , composed of an ldl - c enriched core with one molecular of apolipoprotein b-100 ( apob-100 ) and apolipoprotein(a ) ( apo(a ) ) via a disulfide bond , is currently considered a potential important candidate as supported by previous epidemiological , animal , and genetic epidemiological studies [ 912 ] . in comparison with ldl - c , lp(a ) not only is capable of promoting atherosclerosis , but also has robust effects on enhancing thrombus formation by means of impairing fibrinolysis [ 13 , 14 ] . therefore , lp(a ) elevation is believed to be the very likely risk factor accounting for residual cardiovascular risk , especially in patients with target ldl - c level . nevertheless , findings from previous reported studies and meta - analysis are not consistent [ 1519 ] . for example , some epidemiological studies show that the risk lp(a ) imposes on cardiovascular system is overlapped with ldl - c [ 1618 ] , whereas other studies reveal a quite opposite outcome in which lp(a ) is an independent predictor for cardiovascular risk and traditional risk factor such as ldl - c plays no role in risk estimation for lp(a ) elevation [ 15 , 19 ] . in retrospect , these discrepancies regarding the predictive value of lp(a ) elevation on cardiovascular outcomes may be partially associated with the level of ldl - c which warrants further investigation . nowadays , percutaneous coronary intervention ( pci ) is the preferred choice for revascularization worldwide . however , it is noted that a large number of patients after stent placement , in spite of achieving recommended ldl - c level with statins therapy , have target vessel restenoses which require revascularization . therefore , preventing and reducing the incidence of coronary restenosis after stent placement is of paramount importance . notably , the pathophysiological process of coronary artery restenosis is featured by smooth muscle cells ' overproliferation , endothelial dysfunction , and fibrin accumulation , and with respect to lp(a ) unique features as to proatherosclerosis and prothrombosis , we speculated that lp(a ) elevation might be the potential factor responsible for increased incidence of cardiovascular events , particularly for coronary artery restenosis in patients after stent placement . furthermore , whether the effects of lp(a ) elevation on cardiovascular events ' recurrence after stent placement are dependent on ldl - c level or not would also be investigated . our current study has been registered in the chinese clinical trial registry ( registration number : chictr - och-11001198 ) . written informed consent was obtained and the ethics committee of the guangdong general hospital approved present study . demographic and clinical characteristics of all participants were collected at the initial clinical contact ( see table 1 ) , and all participants were followed up after stent placement via outpatient visit or telephone call for monitoring event occurrence for totally 1 year . accordingly , patient with poststent placement is recommended to achieve target ldl - c level of less than 1.8 mmol / l ; therefore , we used 1.8  mmol / l of ldl - c as cut - off point to categorize all patients into two subgroups . blood samples were drawn by venipuncture in the morning when participants were fasting for at least 8 hours for the variables measurement . of note , plasma level of lp(a ) was measured with sandwich enzyme - linked immune - sorbent assays ( elisa kit , yaji biosystems , shanghai , china ) . all the procedures were performed in accordance with the manual instructions and were evaluated by synchron lx20 unicel dxc800 analyzer ( beckman coulter inc . accordingly , plasma level of lp(a ) lower than 30  mg / dl is considered within the normal range and equal or higher than 30  mg / dl is recognized as abnormal . in our current study , clinical end points after stent placement were defined as cardiovascular death , nonfatal myocardial infarction , nonfatal ischemic stroke , and coronary revascularization . assessment of the incidence of clinical end points after stent placement was performed during followup by means of outpatient visit and/or telephone call after discharge . continuous data was presented as mean  sd or median ( interquartile range ) appropriately and compared by student 's t - test when data was normally distributed , otherwise compared by the wilcoxon rank - sum test . statistical analyses were performed by using spss software version 16.0 ( spss , inc . , as shown in table 1 , the percentages of patients presented with acute coronary syndrome and three vessel stenoses were significantly higher in high lp(a ) group than those in low lp(a ) groups , indicating that patients with lp(a ) elevation were more prone to have more critical coronary artery stenoses . and the percentage of left main coronary artery lesion in high lp(a ) group was higher than that in the low lp(a ) group though without insignificant difference ( 14.3% versus 11.8% , p = 0.321 ) . all participants enrolled in our study were well followed up and were strictly adhering to recommended medications such as dual antiplatelet and statins therapies . selecting ldl - c level of 1.8  mmol / l as the cut - off point , 823 participants were divided into two groups . in the subgroup of ldl - c level lower than 1.8  mmol / l , there were 287 patients with lp(a ) level lower than 30  mg / dl , while another 92 were with lp(a ) level higher than 30  mg / dl . as shown in table 2 , no significant differences of mace were found between low and high lp(a ) groups ( 16.3% versus 18.5% , p = 0.755 ) . and each individual end point between these two groups was also comparable . notably , among each individual outcome , the incidence of coronary revascularization was higher than the others in both groups . another 383 patients with ldl - c level equal or higher than 1.8  mmol / l were divided into two groups according to the cut - off point of lp(a ) . as shown in table 2 , there was significant difference of incident mace after stent placement between high and low lp(a ) groups ( 26.1% versus 16.6% , p = 0.018 ) , and this difference was predominantly derived from the higher incidence of coronary revascularization in high lp(a ) group ( 15.4% versus 7.5% , p = 0.006 ) , and the odds ratio for coronary revascularization in high lp(a ) group was 2.05 , whereas the incidence of the other individual end point was similar between groups . similar to that with ldl - c lower than 1.8  mmol / l , the percentage of coronary revascularization in low and high lp(a ) groups was still higher than other clinical end points , indicating that in poststent placement , target vessel restenosis was the most significant residual cardiovascular risk , regardless of ldl - c level . our study totally enrolled 832 patients diagnosed with coronary artery disease who were eligible for stent placement after coronary angiography examination , and the results showed that ( 1 ) after stent placement , rather than an independent predictor , the predictive value of lp(a ) elevation on cardiovascular outcomes , especially coronary revascularization , was dependent on baseline ldl - c level ; ( 2 ) in the subgroup of baseline ldl - c  1.8  mmol / l , patients with high lp(a ) level have increased incidence of mace than patients with low lp(a ) level , and the between - group difference was mainly derived from coronary revascularization . nevertheless , in the subgroup of baseline ldl - c < 1.8  mmol / l , the incidence of mace after stent placement was comparable between high and low lp(a ) level groups ; ( 3 ) moreover , in comparison to patients with low lp(a ) level , patients with high lp(a ) level more often presented with acute coronary syndrome and three vessel stenoses . currently , percutaneous coronary intervention is broadly applied in patients with significant coronary artery stenosis , and this reperfusion strategy has profoundly improved cardiovascular outcomes in the past two decades . however , accumulating evidence from retrospective and perspective studies shows that , despite stent placement and strictly adhering to contemporary guideline recommended medications , a substantial number of patients still have a high residual cardiovascular risk , especially target vessel restenoses which necessitate revascularization . with respect to these findings , many strategies aiming to reduce residual cardiovascular risk have been introduced , and more aggressive ldl - c lowering is considered as one of the most attractive and promising strategies . in the prove it - timi 22 trial , cannon cp and colleagues observed that in patients with acute coronary syndrome , intensive therapy ( 80  mg of atorvastatin daily ) conferred greater benefits of mortality and mace than those of standard therapy ( 40  mg of pravastatin daily ) , which was believed attributed to further reduction of ldl - c by intensive lipid lowering therapy ( ldl - c 1.60  mmol / l versus 2.46  mmol / l , p < 0.001 ) . however , after nearly 2 years ' followup , the incidence of revascularization in intensive therapy group was still up to 16.3% . additionally , in the ideal and tnt trials , after approximately 5 years ' follow - up , 12.0% and 8.7% of mace were observed , respectively , [ 7 , 8 ] . findings of these large clinical trials consistently show that significant residual cardiovascular risks still remain in patient despise with aggressive ldl - c reduction , and ldl - c alone is inadequate to fully evaluate and predict the residual cardiovascular risk . in lieu of evidence from epidemiological studies [ 2022 ] , lp(a ) elevation has been recognized as a potential candidate at least partially responsible for high residual cardiovascular risk in patient achieving target ldl - c level . however , interaction between lp(a ) and ldl - c on cardiovascular outcome has been observed and whether the effects of lp(a ) elevation on cardiovascular outcome are independent of or dependent on ldl - c is still unclear . our current study showed that the predictive value of lp(a ) elevation for mace , exclusively for coronary revascularization , in chd patients with stent placement is predominantly dependent on baseline level of ldl - c . in the subgroup of baseline ldl - c level  1.8 mmol / l , the incidence of revascularization for patients in high lp(a ) group was significantly increased and the odds ratio was 2.05 when compared to low level group ( 15.4% versus 7.5% , p = 0.006 ) , whereas there was no significant difference of other individual outcome ( see table 2 ) . mmol / l , all cardiovascular outcomes between low and high lp(a ) groups were insignificantly different ( see table 2 ) . accordingly , the key component of lp(a ) in terms of ldl - c enriched core abounds with oxidized phospholipid ( oxpl ) which is a potent proinflammatory and prooxidative compound that can significantly enhance the pro - atherosclerotic potential of lp(a ) , while in patients with extreme low level of ldl - c ( less than 1.8  mmol / l accordingly ) , the risk of lp(a ) elevation on cardiovascular system is diminished or even disappeared , and the underlying mechanisms are not fully understood yet . to our best knowledge , there may be two aspects attributed . in the first place , it was reported that lp(a ) degradation is partially mediated by ldl - c receptor , although the role by this pathway is not fully conclusive yet . therefore , higher ldl - c level may compete for ldl - c receptor which in turn reduces lp(a ) catabolism and amplifies lp(a ) biological effects , and this may be one of the underlying mechanisms attributed to the synergistic effects of both ldl - c and lp(a ) elevations , while in very low ldl - c level ( < 1.8 mmol / l ) , this synergistic effect between ldl - c and lp(a ) may be waned and unappreciated as indicated by our current study and previous studies [ 18 , 21 ] . secondly , it has been identified that , in the normolipidemic individuals , lp(a ) is capable of removing oxidized phospholipids ( such as oxldl - c ) from circulation system via its ability to biding these proinflammatory and prothrombosis materials . therefore , with the higher level of ldl - c , increased lp(a ) level has higher risk of cardiovascular events than that with lower lp(a ) level , while in the lower level of ldl - c , presumed lower oxldl - c level , lp(a ) elevation may be beneficial both for oxldl - c clearance and cardiovascular outcomes , as supported by our current study that , in the subgroup of ldl - c lower than 1.8  mmol / l , the incidence of mace was slightly lower in high lp(a ) group than that in low lp(a ) group ( 16.3% versus 18.5% , p = 0.755 ) , though insignificantly . finally , our current study shows that , in the subgroup of high ldl - c level , the incidence of coronary revascularization after stent placement is positively associated with lp(a ) level . accordingly , lp(a ) is capable of impairing tissue growth factor beta ( tgf- ) activity which results in smooth muscle cells ' proliferation and migration . furthermore , the results from bruneck study support the notion that fibrinolysis attenuation by lp(a ) is crucial for stabilizing atheroma - attached fibrin thrombi . lastly , lp(a ) elevation promotes endothelial dysfunction which also contributes to the restenosis progress . the higher percentage of patients presented with acute coronary syndrome and three vessel stenoses also indicates that the thrombi burden in high lp(a ) groups is greater than that in low lp(a ) group . taken together , it is reasonable to make a conclusion that in patients with stent placement , high lp(a ) level may portend a high restenosis rate . in conclusion , our current study reveals that , in patients with stent placement , lp(a ) elevation is positively associated with coronary restenosis which requires revascularization . in patients with baseline level of ldl - c  1.8 mmol / l , the incidence of mace and coronary revascularization is significantly higher in high lp(a ) group than low lp(a ) group , indicating that , after stent placement , in patient with both baseline levels of ldl - c and lp(a ) elevation , more aggressive ldl - c reduction may mitigate the adverse effects imposed by lp(a ) elevation .
background and aim . incidence of coronary restenosis 
 after stent placement is high . 
 our study was going to investigate whether lp(a ) elevation was potential for predicting coronary restenosis and whether the effects of lp(a ) elevation on coronary restenosis were dependent on ldl - c level . 
 methods and results . 
 totally 832 participants eligible for stent placement were enrolled and followed up for monitoring clinical end points . 
 baseline characteristics were collected . according to the cut point of lp(a ) , participants were divided into low lp(a ) group ( lp(a ) < 30  mg / dl ) and high lp(a ) group ( lp(a )  30  mg / dl ) . furthermore , based on baseline ldl - c level , participants were divided into ldl - c < 1.8  mmol / l and 1.8  mmol / l subgroups . 
 clinical end points including major adverse cardiovascular events ( mace ) , cardiovascular death , nonfatal myocardial infarction , ischemic stroke , and coronary revascularization ( cr ) were compared . 
 patients in high lp(a ) groups more frequently presented with acute coronary syndrome and three vessel stenoses . in subgroup of ldl - c 
 < 1.8  mmol / l , no significant differences of cardiovascular outcomes were found between low and high lp(a ) groups . while in the subgroup of ldl - c  1.8  mmol / l , 
 incidences of mace and cr were significantly higher in high lp(a ) group , and odds ratio for cr was 2.05 . conclusion . with baseline ldl - c and lp(a ) 
 elevations , incidence of cr is significantly increased after stent placement .