Clinical Outcomes In Nondiabetic Patients Research Articles

Empagliflozin effects on iron metabolism as a possible mechanism for improved clinical outcomes in non-diabetic patients with systolic heart failure

Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve clinical outcomes in patients with heart failure (HF), but mechanisms of action are incompletely understood. In the EMPA-TROPISM trial, empagliflozin reversed cardiac remodeling and increased physical capacity in stable non-diabetic patients with systolic HF. Here we explore, post hoc, whether treatment effects in this cohort, comprising patients who had a high prevalence of iron deficiency, were related to iron metabolism. Myocardial iron content estimated by cardiac magnetic resonance T2* quantification increased after initiation of empagliflozin but not placebo (treatment effect: P = 0.01). T2* changes significantly correlated with changes in left ventricular volumes, mass and ejection fraction, peak oxygen consumption and 6-minute walking distance; concomitant changes in red blood cell indices were consistent with augmented hematopoiesis. Exploratory causal mediation analysis findings indicated that changes in myocardial iron content after treatment with empagliflozin may be an important mechanism to explain its beneficial clinical effects in patients with HF.ClinicalTrials.gov: NCT03485222.

Mediation of Systemic Inflammation on Insulin Resistance and Prognosis of Nondiabetic Patients With Ischemic Stroke.

Insulin resistance is associated with stroke recurrence and poor functional outcomes of nondiabetic patients with ischemic stroke. The study aimed to investigate whether the association between insulin resistance and the prognosis of nondiabetic patients with ischemic stroke was mediated by systematic inflammation. Patients with ischemic stroke but without a history of diabetes who were enrolled in CNSR-III (Third China National Stroke Registry) were included in the study and followed up for 1 year after stroke onset. Insulin resistance was determined by using the homeostasis model assessment for insulin resistance (HOMA-IR) method. hs-CRP (high-sensitivity C-reactive protein) and Lp-PLA2 (lipoprotein-associated phospholipase A2) activity were measured at baseline. The primary outcome was stroke recurrence, and other outcomes included composite vascular events, mortality, and poor functional outcome (modified Rankin Scale score, 3-6). Multivariable Cox or logistic regression analyses were performed to estimate the association between HOMA-IR and the study outcomes. A mediation analysis was performed to examine the relationship between insulin resistance and the study outcomes mediated by systemic inflammation. Among a total of 3808 nondiabetic patients with ischemic stroke who were included in the study, the median HOMA-IR was 1.79 (interquartile range, 1.05-2.97). After adjustments for potential confounders, higher HOMA-IR quartiles were associated with higher risks of stroke recurrence, ischemic stroke, and composite vascular events, especially in the large artery atherosclerosis subtype. hs-CRP partially mediated the association between the HOMA-IR index and the prognosis of ischemic stroke (mediation proportion, 5.9% for stroke recurrence and 7.5% for composite vascular events). No evidence of Lp-PLA2 activity mediating the association of insulin resistance with stroke outcomes was observed. Our study found that insulin resistance was associated with poor clinical outcomes in nondiabetic patients with ischemic stroke, which was partially mediated by hs-CRP with a modest amount.

Clinical characteristics and disease outcomes in non-diabetic chronic kidney disease: retrospective analysis of a US healthcare claims database

BackgroundThe observational, real-world evidence FLIEDER study aimed to describe patient clinical characteristics and investigate clinical outcomes in non-diabetic patients with chronic kidney disease (CKD) using data collected from routine clinical practice in the United States.MethodsBetween 1 January, 2008–31 December, 2018, individuals aged ≥ 18 years, with non-diabetic, stage 3–4 CKD were indexed in the Optum® Clinformatics® Data Mart US healthcare claims database using International Classification of Diseases-9/10 codes for CKD or by laboratory values (estimated glomerular filtration rate [eGFR] 15–59 mL/min/1.73 m2). The primary outcomes were hospitalization for heart failure, a composite kidney outcome of end-stage kidney disease/kidney failure/need for dialysis and worsening of CKD stage from baseline. The effects of the intercurrent events of a sustained post-baseline decline in eGFR ≥ 30%, ≥ 40%, and ≥ 57% on the subsequent risk of the primary outcomes were also assessed.ResultsIn the main study cohort (N = 504,924), median age was 75.0 years, and 60.5% were female. Most patients (94.7%) had stage 3 CKD at index. Incidence rates for hospitalization for heart failure, the composite kidney outcome, and worsening of CKD stage from baseline were 4.0, 10.3, and 4.4 events/100 patient-years, respectively. The intercurrent event analysis demonstrated that a relative decline in kidney function from baseline significantly increased the risk of cardiorenal events.ConclusionsThis real-world study highlights that patients with non-diabetic CKD are at high risk of serious adverse clinical outcomes, and that this risk is amplified in patients who experienced greater post-baseline eGFR decline.Graphical abstract

Impact of Pancreatic β-Cell Function on Clopidogrel Responsiveness and Outcomes in Chinese Nondiabetic Patients Undergoing Elective Percutaneous Coronary Intervention.

Insulin resistance and β-cell dysfunction are fundamental defects contributing to type 2 diabetes development. Prior studies indicated that insulin resistance may be correlated with low responsiveness to clopidogrel. This study aimed to investigate the effects of β-cell function on clopidogrel-induced platelet P2Y12 inhibition and the clinical outcomes of nondiabetic patients undergoing elective percutaneous coronary intervention (PCI). Patients scheduled to undergo elective PCI and receive clopidogrel in addition to aspirin were recruited for this study. Homeostatic model assessment 2 of β-cell function (HOMA2-β%) was used to classify participants into quartiles. Thromboelastography (TEG) was used to calculate the quantitative platelet inhibition rate to assess clopidogrel-induced antiplatelet reactivity. The clinical outcome was major adverse cardiovascular and cerebrovascular events (MACCEs). Of the 784 participants evaluated, 21.3% of them (169 of 784) had low responsiveness to clopidogrel. According to multivariate linear regression analysis, the first quartile of HOMA2-β% (19.9-78.1), indicating greater β-cell dysfunction, was independently associated with low responsiveness to clopidogrel compared with the fourth quartile (126.8-326.2) after adjustment for potential covariates [odds ratio 2.140, 95% confidence interval (CI) (1.336 to 3.570), P = 0.038]. In addition, at one year, the first quartile of HOMA2-β% was associated with an increased risk of 1-year MACCE occurrence compared with the fourth quartile [adjusted hazard ratio 4.989, 95% CI (1.571 to 15.845), P = 0.006]. Increased β-cell dysfunction, indicated by a low HOMA2-β%, was associated with low responsiveness to clopidogrel and an increased risk of one-year MACCEs in nondiabetic patients undergoing elective PCI.

Association Between Stress Hyperglycemia Ratio and In-hospital Outcomes in Elderly Patients With Acute Myocardial Infarction.

Backgrounds: Emerging evidence suggests that stress hyperglycemia ratio (SHR), an index of relative stress hyperglycemia, is of great prognostic value in acute myocardial infarction (AMI), but current evidence is limited in elderly patients. In this study, we aimed to assess whether SHR is associated with in-hospital outcomes in elderly patients with AMI.Methods: In this retrospective study, patients who were aged over 75 years and diagnosed with AMI were consecutively enrolled from 2015, January 1st to 2019, December 31th. Admission blood glucose and glycosylated hemoglobin (HbA1C) during the index hospitalization were used to calculate SHR. Restricted quadratic splines, receiver-operating curves, and logistic regression were performed to evaluate the association between SHR and in-hospital outcomes, including in-hospital all-cause death and in-hospital major adverse cardiac and cerebrovascular events (MACCEs) defined as a composite of all-cause death, cardiogenic shock, reinfarction, mechanical complications of MI, stroke, and major bleeding.Results: A total of 341 subjects were included in this study. Higher SHR levels were observed in patients who had MACCEs (n = 69) or death (n = 44) during hospitalization. Compared with a SHR value below 1.25, a high SHR was independently associated with in-hospital MACCEs (odds ratio [OR]: 2.945, 95% confidence interval [CI]: 1.626–5.334, P < 0.001) and all-cause death (OR: 2.871 95% CI: 1.428–5.772, P = 0.003) in univariate and multivariate logisitic analysis. This relationship increased with SHR levels based on a non-linear dose-response curve. In contrast, admission glucose was only associated with clinical outcomes in univariate analysis. In subgroup analysis, high SHR was significantly predictive of worse in-hospital clinical outcomes in non-diabetic patients (MACCEs: 2.716 [1.281–5.762], P = 0.009; all-cause death: 2.394 [1.040–5.507], P = 0.040), but the association was not significant in diabetic patients.Conclusion: SHR might serve as a simple and independent indicator of adverse in-hospital outcomes in elderly patients with AMI, especially in non-diabetic population.

Fasting blood glucose to HDL-C ratio as a novel predictor of clinical outcomes in non-diabetic patients after PCI.

Background The present study was to assess the prognostic value of fasting blood glucose to high-density lipoprotein cholesterol ratio (GHR) in non-diabetic patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI).Methods and results A total of 6645 non-diabetic patients from two independent cohorts, the CORFCHD-PCI study (n=4282) and the CORFCHD-ZZ (n=2363) study, were enrolled in Clinical Outcomes and Risk Factors of Patients with Coronary Heart Disease after PCI. Patients were divided into two groups according to the GHR value. The primary outcome included all-cause mortality (ACM) and cardiac mortality (CM). The average follow-up time was 36.51 ± 22.50 months. We found that there were significant differences between the two groups in the incidences of ACM (P=0.013) and CM (P=0.038). Multivariate Cox regression analysis revealed GHR as an independent prognostic factor for ACM. The incidence of ACM increased 1.284-times in patients in the higher GHR group (hazard ratio [HR]: 1.284 [95% confidence interval [CI]: 1.010–1.631], P<0.05). Kaplan–Meier survival analysis suggested that patients with high GHR value tended to have an increased accumulated risk of ACM. However, we did not find significant differences in the incidence of major adverse cardiac events, main/major adverse cardiovascular and cerebrovascular events (MACCE), stroke, recurrent myocardial infarction (MI) and bleeding events.Conclusions The present study indicates that GHR index is an independent and novel predictor of ACM in non-diabetic CAD patients who underwent PCI.

Prognostic significance of the hemoglobin A1c level in non-diabetic patients undergoing percutaneous coronary intervention: a meta-analysis.

BackgroundThe predictive value of hemoglobin A1c (HbA1c) levels in non-diabetic patients with myocardial infarction undergoing percutaneous coronary intervention (PCI) is still controversial. This study aimed to evaluate whether HbA1c levels were independently associated with adverse clinical outcomes in non-diabetic patients with coronary artery disease (CAD) who had undergone PCI by performing a meta-analysis of cohort studies.MethodsThis meta-analysis included non-diabetic patients with CAD who had undergone PCI. A systematic search for publications listed in the PubMed, Embase, and Cochrane Library databases from commencement to December 2018 was conducted. Studies evaluating the adverse clinical outcomes according to abnormal HbA1c levels in non-diabetic patients diagnosed with CAD who had undergone PCI were eligible. The primary outcomes were long-term all-cause deaths and long-term major adverse cardiac events, and the secondary outcome was short-term all-cause deaths. The meta-analysis was conducted with RevMan 5.3 and Stata software 14.0. Odds ratios (ORs) were pooled using a random or fixed-effects model, depending on the heterogeneity of the included studies. Sub-group analysis or sensitivity analysis was conducted to explore potential sources of heterogeneity, when necessary.ResultsSix prospective cohort studies involving 10,721 patients met the inclusion criteria. From the pooled analysis, abnormal HbA1c levels were associated with increased risk for long-term all-cause death (OR 1.39, 95% confidence interval [CI] 1.16–1.68, P = 0.001, I2 = 45%). Sub-group analysis suggested that abnormal HbA1c levels between 6.0% and 6.5% predicted higher long-term major adverse cardiac event (including all-cause deaths, non-fatal myocardial infarction, target lesion revascularization, target vessel revascularization, recurrent acute myocardial infarction, heart failure requiring hospitalization, and stent thrombosis) risk (OR 2.05, 95% CI 1.46–2.87, P < 0.001, I2 = 0). Contrarily, elevated HbA1c levels were not associated with increased risk of short-term all-cause death (OR 1.16, 95% CI 0.88–1.54, P = 0.300, I2 = 0).ConclusionsAn abnormal HbA1c level is an independent risk factor for long-term adverse clinical events in non-diabetic patients with CAD after PCI. Strict control of HbA1c levels may improve patient survival. Further studies in different countries and prospective cohort studies with a large sample size are required to verify the association.

Impact of Admission Glycated Hemoglobin on Angiographic Characteristics and Short Term Clinical Outcomes of Non-diabetic patients with Acute ST Elevation Myocardial Infarction

Abstract Background Coronary artery disease is the most important cause of death in industrialized countries. Diabetes mellitus is one of the most important modifiable risk factors of coronary artery disease. It increases the risk of coronary artery disease by 2 to 4-fold. Interestingly, this increased risk is not confined to patients with DM, but non-diabetic patients with impaired glucose tolerance (IGT) also may have an increased incidence of cardiovascular complications. Moreover, increased admission glucose levels may be related to a higher mortality rates in patients with acute myocardial infarction (AMI), regardless of diabetic status. Objective To assess the prognostic impact of admission HbA1c in patients without known diabetes mellitus who were admitted with acute ST elevation myocardial infarction, on outcome of 1ry PCI and short-term outcome of adverse cardiac events. Material and Methods This is an observational, this study was conducted at Coronary care unit &amp; coronary catheterization lab unit of cardiology department in Ain Shams University &amp; specialized hospitals. The study period was 6 months (From 1-9-2018 till 1-3-2019). Results 100 patients without prior diagnosis of DM were included in our study population Three categories of patients were created according to HbA1c level: Group 1 (&amp;lt; 5.7%): 46 patients (46%); Group 2 (5.5 to 6.4%): 38patients (38%); Group 3 (&amp;gt;6.5%): 16 patients (16%). Baseline characteristics of the study population are shown in Table 1. The mean age of our sample was 55.06 ± 11.73 years and 96% were males. There was highly statistically significant difference found between DM groups regarding SYNTAX score with P-value (0.002) &amp; another highly significant difference in EF between the 3 groups. Conclusion The present study showed that admission higher HbA1c level in non-diabetic patients presented by acute STEMI is associated with more severe CAD, lower rate of complete revascularization TIMI 3, and higher incidence of adverse cardiac events and mortality. Introducing measurement of HbA1c in the CCU seems to be a simple method to obtain important information on mortality risk.

Glycosylated hemoglobin levels and clinical outcomes in nondiabetic patients with coronary artery disease: A meta-analysis.

A number of studies assessed the prognostic value of HbA1c level in nondiabetic patients with coronary artery disease (CAD). The purpose of this meta-analysis was to assess the association between the HbA1c level and clinical outcomes.We searched PubMed, EMBASE, MEDLINE, and the Cochrane Library from their inception to 10 April 2016. Studies evaluated the outcomes according to HbA1c levels in CAD patients without diabetes mellitus were eligible.Twenty studies involving 22,428 patients were included. In nondiabetic patients with CAD, a high HbA1c level was associated with a higher rate of long-term death (odds ratio 1.76, 95% confidence interval 1.44-2.16, P < .001), and myocardial infarction (MI, odds ratio 1.69, 95% confidence interval 1.07-2.67, P = .026), but not a higher rate of early deaths (odds ratio 1.08, 95% confidence interval 0.92-1.27, P = .359). These findings for death remained the same after sensitivity analyses and the trim and fill method, but the risk difference for MI became nonsignificant after adjustment for potential publication bias.Elevated HbA1c level increased the risks of long-term mortality and MI, but not the risk for early deaths in nondiabetic patients with CAD. High-quality large-scale studies with less bias are needed to confirm these findings.

Impact of Admission Glycosylated Hemoglobin A1c on Angiographic Characteristics and Short Term Clinical Outcomes of Nondiabetic Patients with Acute ST-Segment Elevation Myocardial Infarction.

We aimed to assess the predictive value of admission HbA1c level in nondiabetic patients presented by acute STEMI, on outcome of PCI and short term outcome of adverse cardiac events. Methods. 60 nondiabetic patients were admitted to Cardiology Department, Zagazig University Hospital, with acute STMI: 27 patients with HbA1c levels of 4.5% to 6.4% (group 1), 17 patients with HbA1c levels of 6.5% to 8.5% (group 2), and 16 patients with HbA1c levels higher than 8.5% (group 3). Either invasive intervention was done at admission by (pPCI) or coronary angiography was done within month (3–28 days) from taking thrombolytic. Participants were followed up for 6 months. Results. There was significant difference among different groups of HbA1c as regards the number of diseased vessels, severity of CAD lesions (p value < 0.01), and TIMI flow grades (p value < 0.05). There was significant difference among different groups as regards the adverse cardiac events on short term follow-up period (p value < 0.05). Conclusion. The present study showed that admission higher HbA1c level in patients presented by acute STEMI is associated with more severe CAD, lower rate of complete revascularization, and higher incidence of adverse cardiac events.

Impact of admission glycemia and glycosylated hemoglobin A1c on long-term clinical outcomes of non-diabetic patients with acute coronary syndrome

BackgroundAdmission glucose levels have proven to be a predictor in patients with acute myocardial infarction and elevated glycosylated hemoglobin A1c (HbA1c) is associated with an increased risk of cardiovascular disease, even in patients without diabetes. However, the effect of both admission glucose and HbA1c levels on clinical outcomes in non-diabetic patients with acute coronary syndrome (ACS) has not been fully elucidated. We evaluated the combined effect of admission glucose and HbA1c values on long-term clinical outcomes in non-diabetic patients with ACS treated with percutaneous coronary intervention (PCI). Methods and resultsThis was an observational study of 452 consecutive non-diabetic patients with ACS who underwent PCI between January 1997 and December 2006. The patients were assigned to four groups according to the median values of admission glucose and HbA1c. The primary endpoint comprising a composite of all-cause death and non-fatal MI was compared among the four groups. The primary endpoint occurred in 13.3% of the participants during a median follow-up period of 4.7 years. The cumulative incidence rate of primary endpoint significantly differed among the groups (p=0.048). Multivariable Cox regression analysis showed that the combination of elevated admission glucose and HbA1c was independently associated with long-term clinical outcomes. ConclusionsCombined admission glucose and HbA1c values were independently associated with clinical outcomes in non-diabetic patients with ACS treated with PCI.

Impact of insulin resistance on 1-year clinical outcomes in non-diabetic patients undergoing percutaneous coronary intervention with drug-eluting stents

BackgroundInsulin resistance (IR) is known to be a risk factor for coronary artery disease (CAD). We aimed to evaluate the impact of IR on 1-year clinical outcomes in non-diabetic CAD patients who underwent percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). Methods and resultsA total of 229 consecutive non-diabetic CAD patients treated with DESs were enrolled. Study population was divided into IR group [homeostasis model assessment (HOMA) index≥2.5, n=54] and non-IR group (HOMA index<2.5, n=175). Baseline clinical and procedural characteristics were similar between the groups except higher incidence of high-sensitivity C-reactive protein and lower incidence of multivessel disease as the target vessel in the non-IR group. There was a trend toward longer restenosis lesion length in the IR group at 6 months angiographic follow up but composite major clinical outcomes up to 1 year were similar between the two groups. ConclusionsDespite worse trend in angiographic outcomes in the IR group (HOMA index≥2.5), it was not translated into worse 1-year major clinical outcomes following PCI with DESs as compared to the non-IR group.

AS-203: Impact of Glycosylated Hemoglobin Level on Two-Year Clinical Outcomes in Non-Diabetic Patients Undergoing Elective Percutaneous Coronary Intervention

AS-203: Impact of Glycosylated Hemoglobin Level on Two-Year Clinical Outcomes in Non-Diabetic Patients Undergoing Elective Percutaneous Coronary Intervention

Outcomes in Diabetic and Nondiabetic Patients Treated With Everolimus- or Paclitaxel-Eluting Stents: Results From the SPIRIT IV Clinical Trial (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System)

We compared the safety and efficacy of the XIENCE V (Abbott Vascular, Santa Clara, California) everolimus-eluting stent (EES) with the TAXUS Express (Boston Scientific, Natick, Massachusetts) paclitaxel-eluting stent (PES) among the large cohort of randomized diabetic patients enrolled in the SPIRIT IV (Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System) trial. Diabetes mellitus remains a significant predictor of adverse clinical outcomes after percutaneous coronary intervention with drug-eluting stents, and the comparative outcomes of different drug-eluting stents in diabetic patients remains ill-defined. In the SPIRIT IV trial, 3,687 patients with up to 3 de novo native coronary artery lesions were prospectively randomized 2:1 to receive EES or PES. Randomization was stratified by the presence of diabetes and lesion complexity. The primary end point was the occurrence of target lesion failure (TLF) (cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization) at 1 year. Clinical outcomes were evaluated in randomized diabetic (n = 1,185 [786 EES; 399 PES]) and nondiabetic patients (n = 2,498 [1,669 EES; 829 PES]). The EES compared with PES reduced TLF in nondiabetic patients (3.1% vs. 6.7%, p < 0.0001), with significant reductions in myocardial infarction, stent thrombosis, and target lesion revascularization. In contrast, no difference in TLF (6.4% vs. 6.9%, respectively, p = 0.80) or any of its components was present among diabetic patients, regardless of insulin use. A significant interaction between the presence of diabetes and stent type on TLF (p(interaction) = 0.02) was observed. In the SPIRIT IV randomized trial, EES compared with PES provided similar clinical outcomes in diabetic patients and superior clinical outcomes in nondiabetic patients at 1 year. (SPIRIT IV Clinical Trial: Clinical Evaluation of the XIENCE V Everolimus Eluting Coronary Stent System in the Treatment of Subjects With de Novo Native Coronary Artery Lesions; NCT00307047).

Rosiglitazone could improve clinical outcomes after coronary stent implantation in nondiabetic patients with metabolic syndrome

Recent studies have shown that thiazolidinediones (TZDs) could reduce in-stent restenosis and improve clinical outcomes in patients with type 2 diabetes after coronary stent implantation. It remains unclear whether nondiabetic patients with metabolic syndrome after stenting could also benefit from the treatment with TZDs. Three hundred and sixty patients with metabolic syndrome who underwent coronary stent implantation were randomly assigned to a rosiglitazone group (n = 180) or a control group (n = 180). Patients in the rosiglitazone treatment group were treated with rosiglitazone 1 day before coronary stenting (4 mg once daily) and treatment was continued until the 9 months follow-up; while in the control group, patients were treated with placebo 1 day before the procedure and until the 9 months follow-up. Adverse events were death, myocardial infarction and urgent target vessel revascularization within 9 months after coronary stenting. One hundred and fifty two patients in the rosiglitazone group and 145 patients in the control group survived during the follow-up. Baseline characteristics among patients in the two groups were well balanced. There was no significant difference in target vessels or the procedure of stent implantation. Compared with the control group, treatment with rosiglitazone was associated with a lower rate of death, myocardial infarction and urgent target vessel revascularization (7.2% vs 14.5%, P = 0.044). Rosiglitazone could reduce the risk of the adverse cardiovascular event and improve clinical outcomes in nondiabetic patients with metabolic syndrome after coronary stent implantation.