Lipoprotein(a) and Cardiovascular Outcomes in Patients With Coronary Artery Disease and Prediabetes or Diabetes

Abstract

The aim of the current study is to determine the impact of elevated lipoprotein(a) [Lp(a)] on cardiovascular events (CVEs) in stable coronary artery disease (CAD) patients with different glucose metabolism status. RESEARCH DESIGN AND METHODS In this multicenter study, we consecutively enrolled 5,143 patients from March 2011 to February 2015. Patients were categorized according to status of glucose metabolism (diabetes mellitus [DM], pre-diabetes mellitus [pre-DM], and normal glucose regulation [NGR]) levels and further classified into 12 groups by Lp(a) levels. CVE end points included nonfatal acute myocardial infarction (MI), stroke, and cardiovascular mortality. All subjects were followed up for the occurrence of the CVEs. RESULTS During a median of 6.1 years' follow-up, 435 (8.5%) CVEs occurred. No significant difference in occurrence of CVEs was observed between NGR and pre-DM groups (hazard ratio 1.131 [95% CI 0.822-1.556], P > 0.05). When status of glucose metabolism was incorporated in stratifying factors, 30 £ Lp(a) < 50 mg/dL and Lp(a) ‡50 mg/dL were associated with significantly higher risk of subsequent CVEs in pre-DM (2.181 [1.099-4.327] and 2.668 [1.383-5.415], respectively; all P < 0.05) and DM (3.088 [1.535-5.895] and 3.470 [1.801-6.686], all P < 0.05). Moreover, adding Lp(a) to the Cox model increased the C-statistic by 0.022 and 0.029 in pre-DM and DM, respectively, while the C-statistic was not statistically improved when Lp(a) was included for CVEs prediction in NGR. CONCLUSIONS Our findings, for the first time, indicated that elevated Lp(a) levels might affect the prognosis in patients with pre-DM with stable CAD, suggesting that Lp(a) may help further stratify stable CAD patients with mild impaired glucose metabolism. Lipoprotein(a) [Lp(a)] is an LDL-like particle consisting of a moiety of apolipoprotein(a) bounding covalently to apolipoprotein B-100 (1,2). Plasma Lp(a) induces proatherogenic effects via LDL moiety and prothrombotic effects by the plasminogen-like apolipoprotein(a) (3,4). Strong evidence in epidemiological, genetic, and prospective cohort studies verified that circulating Lp(a) levels were associated with the presence of cardiovascular disease (CVD) (5-7). In the Atherothrombosis

Fibrinogen is associated with glucose metabolism and cardiovascular outcomes in patients with coronary artery disease

“…Patients with CAD but without apparent glucose abnormalities were recommended to evaluate their glycemic state [36]. Prediabetes was associated with a worse prognosis in individuals with stable CAD only when combined with other cardiometabolic disorders [37][38][39]. Several previous studies demonstrated that the measurement of Fib provided incremental value to risk assessment in CAD patients with DM.…”

Prognostic utility of lipoprotein(a) combined with fibrinogen in patients with stable coronary artery disease: a prospective, large cohort study

“…Recently, our data proved that elevated Lp(a) levels were significantly associated with the risk of MACEs in patients with CAD combined with DM or pre-DM [18]. However, for patients with recent ACS who are treated with statins, Lp(a) concentration was not associated with MACEs [19].…”

Prognostic utility of heart-type fatty acid-binding protein in patients with stable coronary artery disease and impaired glucose metabolism: a cohort study

“…As is well known, DM is a worldwide disease results in poor clinical outcomes, and is associated with large health-care costs. Nowadays, pre-DM has been attracted more attention because of its close association with increased cardiovascular risks [7][8][9][10][11]. In our previous studies conducted by Liu et al [9] and Jin et al [10], patients with pre-DM were more likely to have higher CVE risk when combined with other risk such as hypertension.…”

“…The kidney function was measured as estimated glomerular filtration rate (eGFR) using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation: 141 × min(SCr/κ, 1) α × max(SCr/κ, [29]. CAD was defined as the presence of coronary stenosis ≥ 50% at least one major artery segment assessed by two experienced physicians according to the results of CAG as mentioned in our previous studies [10]. The severity of coronary stenosis was assessed as Gensini Score (GS) system, which was defined as 1-point for < 25% stenosis, 2-point for 26-50% stenosis, 4-point for 51-75% stenosis, 8-point for 76-90% stenosis and 32-point for total occlusion.…”

“…Pre-diabetes mellitus (pre-DM) is an intermediate status between normal glucose regulation (NGR) and DM, which is initially considered as a condition associated with the development of DM [4][5][6]. Recently, the attention for pre-DM has significantly been attracted due to its higher risk for coronary artery disease (CAD) and adverse cardiovascular events (CVE) [7][8][9][10][11]. Additionally, besides the atherosclerosis of large arteries can be easily induced by impaired glucose metabolism (IGM), previous studies have also provided the evidence supporting the relation of IGM to myocardial injury and silent ischemia among patients with IGM [12][13][14].…”