To our knowledge, this is the first few studies to evaluate the impact of Lp(a) on coronary artery lesion and in-hospital outcomes in ACS patients undergoing PCI in China. There are two main findings of our current analyses: 1) increased Lp(a) was associated with a more severe coronary artery lesion as reflected by numbers of coronary arteries ≥ 70% stenosis, type C coronary lesion and pre-PCI TIME flow grade 1/0; 2) after adjustment for potential covariates, increased Lp(a) was associated with a higher risk of congestive heart failure and composite in-hospital outcomes. These findings highlight the importance of measuring Lp(a) in ACS patients, which might help to improve cardiovascular risk stratification. With respect to the efficacy of PCSK9 inhibitor on Lp(a) reduction, future researches are needed to evaluate whether PCSK9 inhibitor can reduce in-hospital cardiovascular events in ACS patients with high Lp(a) in Chinese populations.
In ACS patients after PCI treatment, intensive statins has been recommended as the cornerstone treatment. Nonetheless, numerous studies have reported that despite adherence to intensive statins treatment, a substantial proportion of patients remain experience stent thrombosis, myocardial infarction, ischemic stroke/TIA and cardiovascular death. The reasons for the residual cardiovascular risks are likely multifactorial [7, 8, 13, 18], which included systemic inflammation, uncontrolled other risk factors (e.g. hypertension and diabetes), poor adherence to antiplatelet medications, and among others. Importantly, prior studies also have shown that increased Lp(a) is associated with a variety of cardiovascular diseases such as CHD and congestive heart failure [24–26]. The pathophysiological effects of increased Lp(a) on cardiovascular systems are two folds, that is pro-atherosclerosis and pro-thrombosis. Through binding to circulating oxidized phospholipid and apoprotein B100 (OxPL/ApoB100), Lp(a) exerts potent inflammatory and oxidative effects on endothelial cells, causing endothelial dysfunction, macrophages migration and proliferation, foams cells accumulation, and necrotic core expansion [13, 23]. On the other hand, Lp(a) also plays an important role in impairing endogenous fibrinolysis, promoting platelet aggregation and thrombosis formation [13, 23, 27]. These two pathophysiological functions of Lp(a) predispose patients with high Lp(a) at substantial high residual cardiovascular risks. Indeed, prior studies showed that compared to those with low Lp(a), high Lp(a) was associated with more severe coronary artery stenosis as detected by angiography , and was also associated with less coronary collateral circulation in patients with acute myocardial infarction . In addition, one study reported that increased Lp(a) at baseline was associated with a higher risk of stent restenosis and revascularization . Two additional studies also showed that plasma Lp(a) concentration was an independent predictor of stent restenosis [30, 31]. Consistent to prior reports, results of our current study also suggest that in ACS patients undergoing PCI, compared to those with low Lp(a), patients with high Lp(a) had a higher unadjusted risk of acute stent thrombosis, which might be due to the less optimal post-PCI TIMIE flow in these ACS populations. As shown in Table 4 that high Lp(a) was associated with post-PCI TIMI flow grade 1/0, and after adjustment for glycoprotein IIb/IIIa inhibitor, the association was attenuated into statistical insignificance, suggesting that in ACS patients with high Lp(a), use of glycoprotein IIb/IIIa inhibitor during PCI might mitigate the potential thrombotic risk of Lp(a). Future studies are needed to corroborate our findings.
Few studies have reported that increased Lp(a) was associated with a higher risk of congestive heart failure in Caucasian populations. For example, Kamstrup et al reported that elevated Lp(a) level was associated with an increased risk of congestive heart failure . Steffen et al also found that Lp(a)-related risks of congestive heart failure were only evident in Caucasian populations but not in Black or Asian populations . Interestingly and importantly, our current study for the first time showed that compared to those with low Lp(a), patients with high Lp(a) had higher risk of congestive heart failure even after adjustment for potential covariates. The underlying mechanisms are likely multifactorial, and we considered that the higher incidence of congestive heart failure might be due to more severe ischemic injury in ACS patients with high Lp(a). Indeed, patients with high Lp(a) had larger number of coronary stenosis ≥ 70%, were more likely to have type C lesion and left anterior descending coronary stenosis, and poorer coronary perfusion pre- and post-PCI treatment. Further studies are needed to corroborate our current findings and if confirmed, Lp(a) might be used to predict the incidence of congestive heart failure.
There are some limitations of our current study. First, this is a retrospective and observational study, and findings from current study cannot be drawn causal relationship. Second, due to the difference in Lp(a) gene expression between different racial/ethnic populations, current findings might not be extrapolated to other populations. Third, although extensive adjustment for potential covariates, unmeasured and undetected covariates might still exist and influence the association of Lp(a) and outcomes. Fourth, we only evaluated the association of Lp(a) and in-hospital outcomes and whether these observations extended to long-term outcome was unknown. Last but not the least, the modest sample size might not be able to find significant association of high Lp(a) and other cardiovascular events such as myocardial infarction.