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Original article| Volume 76, ISSUE 1, P25-29, July 2020

Prognostic impact of lipoprotein (a) on long-term clinical outcomes in diabetic patients on statin treatment after percutaneous coronary intervention

Open ArchivePublished:February 20, 2020DOI:https://doi.org/10.1016/j.jjcc.2020.01.013

      Highlights

      • We investigated the impact of lipoprotein (a) [Lp(a)] as a residual risk factor.
      • Higher Lp(a) levels were significantly associated with higher rate of major adverse cardiac events.
      • Lp(a) may be a useful risk marker in diabetic patients with statins.

      Abstract

      Background

      Serum levels of lipoprotein (a) [Lp(a)] have been reported as a residual risk marker for adverse events in patients with coronary artery disease (CAD). However, the prognostic impact of Lp(a) on long-term clinical outcomes among diabetic patients on statin therapy after percutaneous coronary intervention (PCI) remains unclear.

      Methods

      The present investigation was a single-center, observational, retrospective cohort study. Among consecutive patients with CAD who underwent first PCI in our institution from 2000 to 2016, we enrolled diabetic patients on statin treatment. As a result, 927 patients (81% men; mean age, 67 years) were enrolled and divided into 2 groups according to a median Lp(a) level of 19.5 mg/dL. The incidence of major adverse cardiac events (MACE), including all-cause death, non-fatal myocardial infarction (MI), and non-fatal cerebral infarction (CI), was evaluated.

      Result

      No significant differences were seen in age, sex, smoking habits, hypertension, chronic kidney disease, or body mass index between high and low Lp(a) groups. During follow-up (median, 5.0 years; interquartile range, 1.9–9.7 years), MACE occurred in 90 cases (17.6%), including 40 (7.9%) cardiac deaths, 18 (3.6%) non-fatal MI, and 37 (7.9%) non-fatal CI. Frequency of MACE was significantly higher in the high-Lp(a) group than in the low-Lp(a) group (log-rank test, p = 0.002). Higher Lp(a) level at the time of PCI was significantly associated with higher frequency of MACE, even after adjusting for other covariates, including other lipid profiles (hazard ratio, 1.91; 95% confidence interval, 1.20–3.09; p = 0.006).

      Conclusion

      Our results demonstrated that in diabetic patients with CAD on statin treatment, increased Lp(a) levels could offer a good residual lipid risk marker. Assessing Lp(a) levels may be useful for risk stratification of long-term clinical outcomes after PCI, especially in diabetic patients.

      Keywords

      Introduction

      Diabetes mellitus (DM) is one of the most prevalent diseases, with an increasing incidence in worldwide. The number of individuals with diabetes is estimated to increase from the current 350 million to 550 million by 2030 [
      • Zimmet P.Z.
      • Magliano D.J.
      • Herman W.H.
      • Shaw J.E.
      Diabetes: a 21st century challenge.
      ]. Although the difference in cardiovascular disease (CVD) risk between DM and non-DM patients has narrowed in recent decades, strong correlations exist between diabetes and CVD events [
      • Sarwar N.
      • Gao P.
      • Seshasai S.R.
      • Gobin R.
      • Kaptoge S.
      • Di Angelantonio E.
      • et al.
      Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies.
      ]. Patients with diabetes are at 2- to 4-fold higher CVD risk compared to those without diabetes [
      • Beckman J.A.
      • Creager M.A.
      • Libby P.
      Diabetes and atherosclerosis: epidemiology, pathophysiology, and management.
      ].
      A number of clinical trials have reported that statin therapy significantly reduced cardiovascular events in patients with coronary artery disease (CAD) [
      Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S).
      ,
      • Okazaki S.
      • Yokoyama T.
      • Miyauchi K.
      • Shimada K.
      • Kurata T.
      • Sato H.
      • et al.
      Early statin treatment in patients with acute coronary syndrome: demonstration of the beneficial effect on atherosclerotic lesions by serial volumetric intravascular ultrasound analysis during half a year after coronary event: the ESTABLISH Study.
      ,
      • Silverman M.G.
      • Ference B.A.
      • Im K.
      • Wiviott S.D.
      • Giugliano R.P.
      • Grundy S.M.
      • et al.
      Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions.
      ]. Although lipid-lowering therapy with statins has seen wide use, CVD risk persists as so-called “residual risk”. Elucidating this residual risk represents an important step toward further prevention of cardiovascular events [
      • Reith C.
      • Armitage J.
      Management of residual risk after statin therapy.
      ].
      Lipoprotein (a) [Lp(a)] comprises a low-density lipoprotein (LDL)-like particle in which apolipoprotein (apo) B is covalently bound by a single disulfide bond to apo(a). Lp(a) has atherothrombotic and proinflammatory properties, with little influence from dietary or environmental factors. Elevated serum Lp(a) is associated with an increased frequency of adverse clinical events among patients with CAD after percutaneous coronary intervention (PCI) [
      • Tsimikas S.
      A test in context: Lipoprotein(a).
      ]. However, the prognostic impact of Lp(a) on long-term clinical outcomes among diabetic patients who underwent PCI with statin therapy remains unclear. We therefore evaluated the association between Lp(a) and long-term outcomes among diabetic patients receiving statins after PCI.

      Methods

      Study design and subject

      The present study was a single-center, observational, retrospective cohort study at Juntendo University Hospital (Tokyo, Japan). Among consecutive patients with CAD who underwent PCI in our institution from 2000 to 2016, we enrolled diabetic patients who were treated with statin therapy at the timing of PCI. Exclusion criteria were as follows: 1) patients with unavailable data on Lp(a); or 2) patients who were undergoing hemodialysis. The study cohort was divided into two groups about the median Lp(a) level (19.5 mg/dL). This study was performed in accordance with the principles of the Declaration of Helsinki.

      Data collection

      Demographic data, coronary risk factors, and medication use were collected from the institutional database. Blood samples were collected during the early morning after an overnight fast. Hypertension was defined as systolic blood pressure (BP) ≥ 140 mmHg, diastolic BP ≥ 90 mmHg, or use of antihypertensive drugs. DM was defined as either hemoglobin (Hb) A1c ≥ 6.5%, medication with oral hypoglycemic drugs, or insulin injections. Estimated HbA1c was calculated as the National Glycohemoglobin Standardization Program equivalent value (%) HbA1c (%) = 1.02 × HbA1c (JDS; %) + 0.25 (%). Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 calculated using the Modification of the Diet in Renal Disease equation modified with a Japanese coefficient using baseline serum creatinine. A current smoker was defined as an individual who was a smoker at the time of PCI or had quit smoking within 1 year before PCI. Indications for PCI were based on objective evidence of myocardial ischemia, ischemic symptoms, or signs associated with significant angiographic stenosis. Lp(a) levels were measured using latex agglutination immunoassays (Special Reference Laboratories, Hachioji, Japan).

      Study endpoints

      The primary endpoint of this study was major adverse cardiac events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal cerebral infarction (CI). Survival data and information about the incident were collected by serial contact with patients or their families and were assessed from the medical records of patients who had died or who had been followed-up at our hospital. Information about the circumstances and date of death were obtained from the families of patients who died at home, and details of events associated with cause of death were supplied by other hospitals or clinics to which the patient had been admitted. All data were collected by blinded investigators. Cardiovascular death was defined as death caused by myocardial infarction, heart failure, or sudden death.

      Statistical analysis

      Continuous variables are expressed as mean ± standard deviation or as median and interquartile range and were compared using one-way analysis of variance or the Kruskal-Wallis test. Baseline data were compared using the paired t-test or Mann-Whitney U test for continuous variables and the chi-square test or Fisher’s exact-test for categorical variables. Unadjusted cumulative event rates were estimated using Kaplan-Meier curves. Factors associated with outcomes were determined using univariable Cox regression analysis including age, sex, hypertension, CKD, dyslipidemia, smoking status, family history of CAD, body mass index (BMI), LDL cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), high-sensitivity C-reactive protein, systolic BP, diastolic BP, left ventricular ejection fraction (LVEF), multivessel disease, acute coronary syndrome (ACS) at presentation, left main trunk lesion, atrial fibrillation, aspirin, β-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers, and high or low Lp(a) levels as independent variables. Model 1 was adjusted for age and sex. Model 2 was adjusted for age and sex plus other variables showing values of p < 0.05 in univariate modeling (CKD and LVEF). Model 3 was adjusted for model 1 and model 2 plus lipid profiles (TG, HDL-C, and LDL-C). The assumption of proportional hazards was assessed using a log-minus-log survival graph. Values of p < 0.05 were considered to indicate statistical significance, unless otherwise indicated. All data were analyzed using JMP version 12.0 for Windows (SAS Institute, Cary, NC, USA).

      Results

      Fig. 1 shows the flow chart of the study population. We analyzed 927 patients with DM who had been treated with statin therapy among 4119 patients who underwent first PCI. Patients for whom Lp(a) data at the time of PCI were unavailable (n = 463) or who were on hemodialysis (n = 251) were excluded. Finally, 927 patients were enrolled and divided into 2 groups according to the median Lp(a) level of 19.5 mg/dL.
      Fig. 1
      Fig. 1Study flow chart. The final cohort for analysis comprised 927 patients assigned to two groups according to median value of Lp(a).
      CAD, coronary artery disease; Lp(a), lipoprotein (a); PCI, percutaneous coronary intervention.
      Table 1 shows the baseline characteristics of patients. LDL-C levels were significantly higher in the high-Lp(a) group than in the low-Lp(a) group. No significant differences were seen in age, sex, smoking habits, hypertension, CKD, or BMI. Median duration of follow-up was 5.0 years (interquartile range, 1.9–9.7 years) and prognostic data were fully documented during the entire follow-up period. During follow-up, 90 (17.6%) primary endpoints occurred, including 40 (7.9%) cardiac deaths, 18 (3.6%) non-fatal MIs, and 37 (7.9%) non-fatal CIs. Fig. 2 shows cumulative incidence curves for MACE. The frequency of MACE was significantly higher in the high-Lp(a) group than in the low-Lp(a) group (log-rank test, p = 0.002).
      Table 1Baseline characteristics of the study population.
      Overall (n = 927)High Lp(a) (n = 465)Low Lp(a) (n = 462)p
      Lp(a), mg/dL19.5 (10.0–34.2)34.0 (26.0–53.7)10.0 (5.0–14.0)<0.0001
      Age, years66.5 ± 10.065.0 ± 9.767.1 ± 10.40.06
      Male, n (%)751 (81.0)366 (78.7)385 (83.3)0.07
      Hypertension, n (%)704 (75.9)351 (75.5)353 (76.4)0.74
      CKD, n (%)232 (25.0)125 (26.9)107 (23.2)0.19
      Dyslipidemia, n (%)789 (85.1)394 (84.7)395 (85.5)0.74
      Current smoking, n (%)235 (25.4)119 (25.6)116 (25.2)0.88
      Family history of CAD, n (%)276 (29.8)144 (31.0)132 (28.6)0.44
      BMI, kg/m224.9 ± 3.724.8 ± 3.824.9 ± 3.50.69
      HbA1c,7.2 ± 1.27.2 ± 1.37.2 ± 1.10.62
      TG, mg/dL142.8 ± 118.0137.1 ± 131.6148.5 ± 102.30.14
      HDL-C, mg/dL43.5 ± 13.343.6 ± 14.543.5 ± 12.00.90
      LDL-C, mg/dL102.0 ± 33.9106.3 ± 33.797.6 ± 33.5<0.0001
      hsCRP, mg/L1.1 (0.4–3.3)1.2 (0.5–3.7)1.0 (0.4–2.7)0.85
      BNP, pg/dL40.7 (20.2–96.2)39.7 (20.5–108.7)41.5 (19.7–173.4)0.54
      Systolic BP, mmHg138.1 ± 22.6137.8 ± 23.5138.6 ± 21.60.59
      Diastolic BP, mmHg74.1 ± 13.673.8 ± 13.374.3 ± 13.80.60
      LVEF, %61.3 ± 12.560.8 ± 13.261.7 ± 11.70.29
      Multivessel disease, n (%)584 (63.5)300 (64.9)284 (62.1)0.38
      Presentation of ACS, n (%)190 (20.5)89 (19.1)101 (21.9)0.31
      LMT lesion, n (%)33 (3.6)18 (3.9)15 (3.3)0.61
      Atrial fibrillation, n (%)25 (9.1)11 (8.9)14 (9.4)0.88
      Medication
       Aspirin, n (%)903 (97.4)452 (97.2)451 (97.6)0.69
       β-blocker, n (%)476 (51.5)235 (50.5)241 (52.4)0.57
       CCB, n (%)373 (40.3)178 (38.4)195 (42.4)0.21
       ACE-I/ARB, n (%)534 (57.7)268 (57.6)266 (57.8)0.95
      Follow up (6–9 months apart)
       Lp(a), mg/dL19.4 (9.0–34.0)34.0 (25.0–55.8)9.0 (5.0–14.0)<0.0001
      CKD, chronic kidney disease; CAD, coronary artery disease; BMI, body mass index; TG, triglyceride; HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol; hsCRP, high-sensitivity C-reactive protein; Lp(a), lipoprotein (a); BP, blood pressure; LVEF, left ventricular ejection fraction; ACS, acute coronary syndrome; LMT, left main trunk; BNP, B-type natriuretic peptide; CCB, calcium channel blocker; ACE-I, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker.
      Fig. 2
      Fig. 2Kaplan-Meier curve for MACE (DM). The frequency of MACE was significantly higher in the high-Lp(a) group than in the low-Lp(a) group (log-rank test, p = 0.002).
      DM, diabetes mellitus; Lp(a), lipoprotein (a); MACE, major adverse cardiac events.
      Table 2 shows the results of Cox proportional hazard regression analysis for MACE. The high-Lp(a) group showed a significantly higher frequency of MACE than the Low-Lp(a) group [hazard ratio (HR), 1.83; 95% confidence interval (CI) 1.16–2.95; p = 0.009], even after adjusting for other risk factors (age, sex, CKD, LVEF, TG, HDL-C, and LDL-C). The log-transformed variable Lp(a) was also related to the frequency of MACE (HR, 1.31; 95%-CI, 1.03–1.67; p = 0.026).
      Table 2Cox proportional hazard models for MACE.
      HR95%CIp-value
      Lp(a) as categorical variable [high vs. low Lp(a) group]
       Crude1.981.29–3.130.002
       Model 12.091.35–3.13<0.001
       Model 21.921.23–3.070.004
       Model 31.831.16–2.950.009
      Lp(a) as log-transformed variable (HR per 1 increase)
       Crude1.361.09–1.730.007
       Model 11.411.12–1.790.003
       Model 21.331.05–1.690.016
       Model 31.311.03–1.670.026
      Model 1: adjusted for age and sex.
      Model 2: adjusted for age, sex, chronic kidney disease, and left ventricular ejection fraction.
      Model 3: adjusted for age, sex, chronic kidney disease and left ventricular ejection fraction, triglyceride, HDL-C, and LDL-C.
      HR, hazard ratio; 95%CI, 95% confidence interval; Lp(a), lipoprotein (a); MACE, major adverse cardiac events; HDL-C, high-density lipoprotein-cholesterol; LDL-C, low-density lipoprotein-cholesterol.

      Discussion

      The major findings of the present study, as an observational study evaluating the impact of Lp(a) levels in diabetic CAD patients on statin therapy, were as follows: 1) median Lp(a) in this Asian population tended to be lower than levels reported from Western countries; 2) LDL-C levels were significantly higher in the high-Lp(a) group than in the low-Lp(a) group; 3) patients with high Lp(a) showed a significantly higher frequency of MACE than those with low Lp(a); and 4) even after adjusting for clinically important covariates, high Lp(a) was independently associated with poorer long-term clinical outcomes among diabetic CAD patients receiving statins.
      Although there is a 2- to 4-fold higher risk of CAD in patients with diabetes, whether diabetes represents a true biomarker remains contentious [
      • Franco O.H.
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      • Hu F.B.
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      • Nusselder W.
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      ]. Riddle et al. reported that aggressive lowering of blood glucose failed to further decrease CVD [
      • Riddle M.C.
      Effects of intensive glucose lowering in the management of patients with type 2 diabetes mellitus in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.
      ]. Mendelian randomization has reported whether an association of a biomarker with CAD is a causal or true risk factor. DM itself has been suggested to not represent a true risk factor, but is merely a biomarker [
      • Jansen H.
      • Samani N.J.
      • Schunkert H.
      Mendelian randomization studies in coronary artery disease.
      ]. Clarification of what true biomarkers correlate with CVD events in diabetic patients is thus very important. The present study found no significant association between Lp(a) value and frequency of MACE among non-DM patients (Fig. 3).
      Fig. 3
      Fig. 3Kaplan-Meier curve for MACE (non-DM).
      No significant association was evident between Lp(a) values and frequency of MACE in non-DM patients (p = 0.50).
      DM, diabetes mellitus; Lp(a), lipoprotein (a); MACE, major adverse cardiac events.
      Lp(a) is an LDL-like particle with an apo(a) moiety covalently bound to the apoB component [
      • Tsimikas S.
      A test in context: Lipoprotein(a).
      ,
      • Nordestgaard B.G.
      • Langsted A.
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      ]. Lp(a) levels are determined by the LPA gene locus and are not significantly affected by diet or environmental factors [
      • Kronenberg F.
      Human genetics and the causal role of lipoprotein(a) for various diseases.
      ]. The atherogenicity of Lp(a) is broadly classified into 3 categories: proatherogenic effects of the LDL-like moiety; the proinflammatory effects of the oxidized phospholipid content; and the potentially antifibrinolytic effects of the apo(a) moiety [
      • Spence J.D.
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      ]. Previously, Lp(a) has been considered a weak risk factor with substantial LDL-C reductions [
      • Maher V.M.
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      • Marcovina S.M.
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      • Zhao X.Q.
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      ]. Nevertheless, the prognostic value among individuals with low LDL-C levels remains unclear due to heterogeneity across trials [
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      ]. A recent meta-analysis suggested that an elevated Lp(a) (>50 mg/dL) was associated with increased risk of MACE in patients on statin therapy [
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      ]. The cut-off Lp(a) level of these previous studies was higher than that in Japanese patients [
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      ]. In this study of a Japanese population, median Lp(a) value was lower than reported in Western countries. Despite this low value, significant correlation with CVD outcomes was identified.
      Statin therapy targeting LDL-C markedly reduced CVD events in both primary and secondary prevention. In a serial intravascular ultrasound study, it was reported that statin treatment and achievement of LDL-C <70 mg/dL were associated with plaque regression and lower rate of adverse cardiac events [
      • Endo H.
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      ]. Although therapies to strongly reduce LDL-C have been shown to prevent CVD events, eliminating all CVD events is not possible, leaving a residual risk [
      • Silverman M.G.
      • Ference B.A.
      • Im K.
      • Wiviott S.D.
      • Giugliano R.P.
      • Grundy S.M.
      • et al.
      Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions.
      ,
      • Reith C.
      • Armitage J.
      Management of residual risk after statin therapy.
      ]. Statins have been considered to have no effect on Lp(a) levels, because LDL receptors may play no or only a minor role in Lp(a) clearance. However, in a recent analysis, mean Lp(a) level after statin therapy (including atorvastatin, rosuvastatin, and pitavastatin) was increased by 11% compared to pre-statin therapy [
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      ]. Risk stratification is therefore required for patients on statins. The mechanisms by which statins increase Lp(a) levels are unclear, and require further investigation.
      Other therapies including niacin, microsomal triglyceride transfer protein inhibitors and cholesteryl ester transfer protein (CETP) inhibitors all lower Lp(a) levels to varying degrees. Niacin, PCSK9 inhibitors, and CETP inhibitors decrease levels by 20–30%. Apheresis results in a time-averaged reduction of 30–35%. Antisense oligonucleotides (ASOs) reduce Lp(a) by 80–99% [
      • Tsimikas S.
      A test in context: Lipoprotein(a).
      ]. However, randomized controlled trials have not been reported and their clinical use remains limited [
      • Ellis K.L.
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      ]. Currently, the most promising drug therapies for lowering Lp(a) are PCSK9 inhibitor and ASOs. Evolocumab significantly reduced Lp(a) levels by 26.9% from baseline to 48 weeks [
      • Sabatine M.S.
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      ]. However, Ray et al. reported that Lp(a) reductions were not significantly associated with MACE independently of LDL-C reductions in phase 3 ODYSSEY trials [
      • Ray K.K.
      • Vallejo-Vaz A.J.
      • Ginsberg H.N.
      • Davidson M.H.
      • Louie M.J.
      • Bujas-Bobanovic M.
      • et al.
      Lipoprotein(a) reductions from PCSK9 inhibition and major adverse cardiovascular events: Pooled analysis of alirocumab phase 3 trials.
      ]. ASOs reduce Lp(a) by reducing the production of apo(a) via inhibition of mRNA translation, which offers greater specificity compared with PCSK9 inhibitor [
      • Graham M.J.
      • Viney N.
      • Crooke R.M.
      • Tsimikas S.
      Antisense inhibition of apolipoprotein (a) to lower plasma lipoprotein (a) levels in humans.
      ]. Further clinical trials would provide some clues to Lp(a)-targeted therapy with statins.
      Currently, statin therapy is used broadly, according to the recent European Society of Cardiology and American College of Cardiology/American Heart Association guidelines [
      • Grundy S.M.
      • Stone N.J.
      • Bailey A.L.
      • Beam C.
      • Birtcher K.K.
      • Blumenthal R.S.
      • et al.
      2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol.
      ,
      • Mach F.
      • Baigent C.
      • Catapano A.L.
      • Koskinas K.C.
      • Casula M.
      • Badimon L.
      • et al.
      2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk.
      ]. However, Lp(a) has been suggested to be elevated by statin administration. Thus, risk stratification of the population under statin treatment by Lp(a) appears important. Those patients for whom Lp(a) should be measured or interventions provided are uncertain. In this study, no significant correlation was observed in non-DM patients, and a significant correlation was observed in the DM patient group, despite low Lp(a) levels. In primary prevention of CAD in DM patients, Waldeyer et al. revealed that hazard ratios for Lp(a) were not significantly different among subgroups defined by age, sex, smoking, hypertension, BMI, region, and LDL-C, but were significantly higher in DM [
      • Waldeyer C.
      • Makarova N.
      • Zeller T.
      • Schnabel R.B.
      • Brunner F.J.
      • Jorgensen T.
      • et al.
      Lipoprotein(a) and the risk of cardiovascular disease in the European population: results from the BiomarCaRE consortium.
      ]. However, in the field of a secondary prevention, it is unclear that high Lp(a) associates with adverse cardiovascular events in patients with DM. Proinflammatory conditions, antifibrinolytic effects, and endothelial dysfunction are important features of atherosclerotic process observed in DM patients, which is also triggered by Lp(a) [
      • Biondi-Zoccai G.G.
      • Abbate A.
      • Liuzzo G.
      • Biasucci L.M.
      Atherothrombosis, inflammation, and diabetes.
      ]. In addition, serum Lp(a) levels promote inflammation and lead to insulin resistance [
      • Onat A.
      • Donmez I.
      • Karadeniz Y.
      • Cakir H.
      • Kaya A.
      Type-2 diabetes and coronary heart disease: common physiopathology, viewed from autoimmunity.
      ]. These might indicate that high Lp(a) with DM contributed to worse outcomes. This study suggests that in patients on statin treatment, Lp(a) should be measured in DM patients and further intervention should be considered.
      Several limitations of this study require consideration. First, this was a single-center, observational study of a small cohort, and other unknown confounding factors might have affected the outcomes regardless of analytical adjustments. Second, relatively few events occurred during follow-up, resulting in the absence of statistically significant differences in outcome measures. Finally, the choice or dose of statin depended on the individual physicians and we had no information about patient compliance with prescribed medical therapy during follow-up.

      Conclusions

      Lp(a) value was significantly associated with CVD events, despite low levels compared to previous studies from Western countries. Lp(a) could represent a residual risk marker among diabetic patients receiving statin therapy after PCI in Asian populations.

      Conflict of interest

      None declared.

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