Jeong Yoon Jang

Novel role of platelet reactivity in adverse left ventricular remodelling after ST-segment elevation myocardial infarction: The REMODELING Trial

The role of platelet-leukocyte interaction in the infarct myocardium still remains unveiled. We aimed to determine the linkage of platelet activation to post-infarct left ventricular remodelling (LVR) process. REMODELING was a prospective, observational, cohort trial including patients (n = 150) with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. Patients were given aspirin plus clopidogrel therapy (600 mg loading and 75 mg daily). Platelet reactivity (PRU: P2Y12 Reaction Units) was assessed with VerifyNow P2Y12 assay on admission. Transthoracic echocardiography was performed on admission and at one-month follow-up. The primary endpoint was the incidence of LVR according to PRU-based quartile distribution. LVR was defined as a relative ≥ 20 % increase in LV end-diastolic volume (LVEDV) between measurements. Adverse LVR was observed in 36 patients (24.0 %). According to PRU quartile, LVR rate was 10.8 % in the first, 23.1 % in the second, 27.0 % in the third, and 35.1 % in the fourth (p = 0.015): the optimal cut-off of PRU was ≥ 248 (area under curve: 0.643; 95 % confidence interval: 0.543 to 0.744; p = 0.010). LVR rate also increased proportionally according to the level of high sensitivity-C reactive protein (hs-CRP) (p = 0.012). In multivariate analysis, the combination of PRU (≥ 248) and hs-CRP (≥ 1.4 mg/l) significantly increased the predictive value for LVR occurrence by about 21-fold. In conclusion, enhanced levels of platelet activation and inflammation determined the incidence of adverse LVR after STEMI. Combining the measurements of these risk factors increased risk discrimination of LVR. The role of intensified antiplatelet or anti-inflammatory therapy in post-infarct LVR process deserves further study.

Long-term Prognosis and Clinical Characteristics of Patients with Newly Diagnosed Diabetes Mellitus Detected after First Acute Myocardial Infarction: from KAMIR-NIH Registry

Background and Objectives After the first acute myocardial infarction (AMI), a considerable proportion of patients are newly diagnosed with diabetes mellitus (DM). However, in AMI, controversy remains regarding the disparity in prognosis between previously diagnosed DM (known-DM) and newly diagnosed DM (new-DM). Methods The study included 10,455 patients with AMI (non-DM, 6,236; new-DM, 659; known-DM, 3,560) admitted to one of 15 participating centers in Korea between November 2011 and January 2016 (average follow-up, 523 days). We compared the characteristics and clinical course of patients with known-DM and those with new- or non-DM. Results Compared to patients with known-DM, those with new-DM or non-DM were younger, more likely to be male, and less likely to have hypertension, dyslipidemia, prior stroke, angina, or myocardial infarction. Compared to patients with new-DM or non-DM (reference), those with known-DM had higher risks of major adverse cardiac events (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.06–1.35; p=0.004), cardiac death (HR, 1.26; 95% CI, 1.01–1.57; p=0.042), and congestive heart failure (HR, 1.58; 95% CI, 1.20–2.08). Unlike known-DM, new-DM did not increase the risk of cardiac events (including death). Conclusions Known-DM was associated with a significantly higher risk of cardiovascular events after AMI, while new-DM had a similar risk of cardiac events as that noted for non-DM. There were different cardiovascular outcomes according to diabetes status in patients with AMI.

Prognostic value of brachial-ankle pulse wave velocity in patients with non-st-elevation myocardial infarction

Objective Brachial-ankle pulse wave velocity (baPWV) measurement is a well-established modality for assessing arterial stiffness and predicting cardiovascular events. However, to our knowledge, its usefulness has not been clarified among patients with non-ST-elevation myocardial infarction (NSTEMI). This study assessed the prognostic value of baPWV in patients with NSTEMI. Patients and methods Patients (n=411, mean age, 63.8±13.5 years, 75.2% men) with NSTEMI who underwent a percutaneous coronary intervention and baPWV measurement were recruited between January 2013 and December 2015. Cardiac mortality and major adverse cardiovascular events (MACE) including cardiac death, re-acute myocardial infarction, revascularization, heart failure, and stroke after discharge were analyzed. The mean follow-up duration was 350 days. Results MACE and cardiac mortality occurred in 26 (6.3%) patients and 13 (3.1%) patients. Kaplan–Meier survival curves showed that MACE and cardiac mortality were significantly higher in patients with high baPWV (1708.0 cm/s). In multivariable Cox regression analysis, high baPWV (hazard ratio: 2.55; 95% confidence interval: 1.03–6.30, P=0.043) was an independent predictor of MACE even after adjusting for possible confounders. Conclusion Our findings indicate that baPWV was a strong independent prognostic factor of MACE in patients with NSTEMI. This suggests that baPWV can be a useful prognostic factor in the clinical setting for easier and less invasive prediction of MACE in patients with NSTEMI.

Pharmacodynamic effects of a new fixed-dose clopidogrel–aspirin combination compared with separate administration of clopidogrel and aspirin in patients treated with coronary stents: The ACCEL-COMBO trial

Abstract Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is a widely prescribed regimen to prevent ischemic events in patients undergoing percutaneous coronary intervention (PCI). A fixed-dose combination (FDC) capsule (HCP0911) has been developed to provide dosing convenience and improve adherence. We compared the antiplatelet effects of single daily dose HCP0911 with separate treatment with daily 75 mg clopidogrel plus 100 mg aspirin. This was a randomized, open-label, two-period, crossover, non-inferiority study conducted in stented patients who had been treated for at least 6 months with clopidogrel and aspirin. Thirty patients were randomly assigned to receive either daily 75 mg clopidogrel plus 100 mg aspirin treatment or HCP0911 for 2 weeks and then were crossed over to the other treatment for 2 weeks. Pharmacodynamic effects were measured with VerifyNow, light transmittance aggregometry (LTA), and thromboelastography (TEG®). The primary endpoint was P2Y12 Reaction Units (PRU) measured by VerifyNow. PRUs during treatment with HCP0911 were not inferior to those during separate treatment (202 ± 52 vs. 207 ± 60 PRU; mean difference, −5 PRU; 90% confidence interval of difference, −23 to 13 PRU; P for non-inferiority = 0.015 for predetermined limit). “BASE” and Aspirin Reaction Units by VerifyNow did not differ between the two treatments. During each treatment, there were no differences in maximal and final platelet aggregations by LTA (all P values ≥0.822) and TEG® measurements. In conclusion, in stented patients, the antiplatelet effect of a fixed-dose clopidogrel–aspirin combination, HCP0911, was not inferior to separate administration of clopidogrel and aspirin.

Antiplatelet Therapy Combinations and Thrombogenicity in Patients with Non-Valvular Atrial Fibrillation

Background and Objectives Combination antiplatelet therapy reduces the risk of ischemic stroke compared with aspirin monotherapy in non-valvular atrial fibrillation (NVAF) patients. The underlying mechanism, however, remains unclear. In addition, the association between platelet inhibition and thrombogenicity in NVAF has not been evaluated. Subjects and Methods We randomized 60 patients with NVAF that were taking 100 mg of aspirin daily (>1 month) to adding 75 mg of clopidogrel daily (CLPD group), 100 mg of cilostazol twice daily (CILO group), or 1000 mg of omega-3 polyunsaturated fatty acid twice daily (PUFA group). Biomarkers (von Willebrand factor antigen [vWF:Ag], fibrinogen, D-dimer, and high-sensitivity C-reactive protein [hs-CRP]) and platelet reactivity (PR), which were the levels stimulated by adenosine diphosphate (ADP), thrombin-receptor agonist peptide, collagen, and arachidonic acid, were measured at baseline and 30-day follow-up. Results Combination antiplatelet therapy significantly reduced vWF:Ag and fibrinogen levels (7.7 IU/dL, p=0.015 and 15.7 mg/dL, p=0.005, respectively), but no changes were found in D-dimer and hs-CRP levels. The CLPD and CILO groups showed fibrinogen and vWF:Ag level reductions (24.9 mg/dL, p=0.015 and 9.3 IU/dL, p=0.044, respectively), whereas the PUFA group did not show any differences in biomarkers. Irrespective of regimen, the changes in fibrinogen and vWF:Ag levels were mainly associated with the change in ADP-mediated PR (r=0.339, p=0.008 and r=0.322, p=0.012, respectively). Conclusion In patients with NVAF, combination antiplatelet therapy showed reductions for vWF:Ag and fibrinogen levels, which may be associated with the inhibitory levels of ADP-mediated PR. The clinical implications of these findings need to be evaluated in future trials.

TICAGRELOR VERSUS CLOPIDOGREL IS ASSOCIATED WITH BETTER RECOVERY OF LV FUNCTION AFTER ACUTE MYOCARDIAL INFARCTION

Background: Recovery of LV function following AMI is associated with the risk of long-term CV mortality and CHF progression. We sought to evaluate the predictors of recovery of LV function in AMI patients. Methods: AMI patients treated with uneventful PCI were prospectively enrolled (n=224). At 30-

Association between pulse pressure and body mass index in hypertensive and normotensive populations in the Korea National Health and Nutrition Examination Survey V, 2010–2012

The authors conducted a national cross‐sectional cohort study to evaluate the associations between pulse pressure (PP) and body mass index (BMI) and sex, according to blood pressure (BP) status. A total of 18 812 patients without a history of antihypertensive medication and cardiovascular disease were selected. There was good concordance between PP and the selected cardiovascular risk factors. PP increased with high BMI among patients with normal BP, but decreased with high BMI among patients with hypertension (HTN). BMI (ß, −0.260; SE, 0.039 [P<.001]) and male sex (ß, −4.727; SE, 1.100 [P<.001]) were negatively correlated with PP in a multivariate model adjusted for several risk factors in patients with HTN. In conclusion, PP was negatively correlated with BMI in patients with HTN, which may explain the higher cardiovascular risk in lean persons and women with HTN.