Lipoprotein (a) predicts recurrent worse outcomes in type 2 diabetes mellitus patients with prior cardiovascular events: a prospective, observational cohort study

Abstract

Background: Merging studies have reported the association of lipoprotein(a) [Lp(a)] with poor outcomes of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). However, the prognostic importance of Lp(a) for recurrent cardiovascular events (CVEs) is currently undetermined in patients with T2DM and prior CVEs. Methods: From April 2011 to March 2017, we consecutively recruited 2284 T2DM patients with prior CVEs. Patients were categorized into low, medium, and high groups by Lp(a) levels and followed up for recurrent CVEs, including nonfatal acute myocardial infarction, stroke, and cardiovascular mortality. Kaplan-Meier, Cox regression and C-statistic analyses were performed. Results: During 7613 patient-years' follow-up, 153 recurrent CVEs occurred. Lp(a) levels were significantly higher in patients with recurrent CVEs than counterparts (20.44 vs. 14.71 mg/dL, p = 0.002). Kaplan-Meier analysis revealed that the event-free survival rate was dramatically lower in high and medium Lp(a) groups than that in low group irrespective of HBA1c status (< 7.0%; ≥ 7.0%, both p < 0.05). Furthermore, multivariate Cox regression models indicated that Lp(a) was independently associated with high risk of recurrent CVEs [HR(95% CI): 2.049 (1.308-3.212)], such data remains in different HBA1c status (HR(95% CI): < 7.0%, 2.009 (1.051-3.840); ≥ 7.0%, 2.162 (1.148-4.073)). Moreover, the results of C-statistic were significantly improved by 0.029 when added Lp(a) to the Cox model. Conclusions: Our data, for the first time, confirmed that Lp(a) was an independent predictor for recurrent CVEs in T2DM patients with prior CVEs, suggesting that Lp(a) measurement may help to further risk stratification for T2DM patients after they suffered a first CVE.

Lipoprotein(a) and Cardiovascular Disease in Chinese Population

“…The results showed that when CVD was combined with T2DM, the cardiovascular risks associated with Lp(a) might further increase. 35 There are also occasional reports indicating that increased Lp(a) levels are associated with arterial calcification and venous thrombotic disease, but more evidence is needed to confirm this finding.…”

Diabetic dyslipidemia impairs coronary collateral formation: An update

“…Noteworthy, Lp (a) is known to have atherothrombogenic property by inhibiting fibrinolysis system and promoting thrombus formation. In spite of a very skewed distribution, elevated circulating Lp(a) has emerged as an independent predictor of adverse outcomes for both general and higher risk populations, especially when LDL-C levels are elevated ( 32 ). In observational studies of patients with stable CAD, serum Lp(a) levels decreased stepwise across angiographic coronary collateral grade, and elevated Lp(a) predicted poor collateral development ( 33 , 34 ).…”

High lipoprotein(a) concentrations are associated with lower type 2 diabetes risk in the Chinese Han population: a large retrospective cohort study

“…Several large-scale cohort studies have shown an inverse association between T2DM risk and Lp(a) levels, which has not been validated through Mendelian randomization trials [ 11 – 13 ]. A limited number of studies have explored this association in Asian populations, with inconsistent results [ 14 , 15 ]. Therefore, this study aimed at exploring the association between Lp(a) concentrations and T2DM, and to evaluate potential modification factors in the Chinese population.…”