Abstract P023: Relationship Between Vitamin D Status and Incidence of Macro-vascular Events in the Veterans Affairs Diabetes Trial (VADT)

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Jimmy D Alele ◽  
Kelly J Hunt ◽  
Bruce W Hollis ◽  
Deirdre K Luttrell ◽  
Louis M Luttrell ◽  
...  

BACKGROUND: Few studies have examined the relationship between vitamin D levels and incident cardiovascular events in large well-characterized type 2 diabetes cohorts. METHODS: We performed prospective analyses to determine associations between vitamin D status and vascular endpoints among 936 Veterans Affairs Diabetes Trial (VADT) participants (mean age 59.7 years; 96.7% male; 40.4% minority). 25 (OH)-vitamin D was measured a median of two years after entry into the VADT study and participants were subsequently followed an average of 3.7 years for outcomes. Cox proportional hazard models were used to calculate hazard ratios (HRs) for macrovascular endpoints in relation to vitamin D quartile. The primary composite endpoint included documented myocardial infarction; stroke; death from cardiovascular causes; new or worsening congestive heart failure; surgical intervention for cardiac, cerebrovascular, or peripheral vascular disease; inoperable coronary artery disease; and amputation for ischemic gangrene. RESULTS: On average VADT participants had high cardiovascular risk at entry into the study: 65.3% of the patients recruited were obese, 38.5% had previously had a vascular event, 78.7% had hypertension and 59.5% were using statins. During follow-up, 17.2%, 5.0%, 5.9%, 2.4% and 6.6% of participants had a primary composite endpoint, myocardial infarction, chronic heart failure, cardiovascular death or all-cause death, respectively. After adjusting for age, minority status, treatment arm and history of prior event, individuals in the lowest quartile of vitamin D (i.e., 1 to 15.9 ng/ml) were at similar risk of the primary composite endpoint [HR=1.26 (95% CI: 0.81, 1.96)], myocardial infarction [HR=1.13 (95% CI: 0.53, 2.42)], congestive heart failure [HR=1.44 (95% CI: 0.67, 3.06)], cardiovascular death [HR=0.86 (95% CI: 0.28, 2.63)], and death from any cause [HR=1.04 (95% CI: 0.53, 2.04)] as individuals in the highest quartile of vitamin D (i.e., 29.9 to 77.2 ng/ml). CONCLUSIONS: These data indicate that vitamin D status had no significant impact on the incidence of macrovascular events in a cohort of high-risk veterans with type 2 diabetes mellitus in which traditional risk factors were managed according to current treatment guidelines. SUPPORT: This work was supported by American Heart Association Grant-in-Aid AHA0755466U and the Research Service of the Charleston SC VA Medical Center.

Author(s):  
Mei-Zhen Wu ◽  
Yan Chen ◽  
Yu-Juan Yu ◽  
Zhe Zhen ◽  
Ying-Xian Liu ◽  
...  

Abstract Aims  Few prospective studies have evaluated sex-specific pattern, natural progression of left ventricular (LV) remodelling, and diastolic dysfunction in patients with type 2 diabetes (T2DM). The aim of this study was to study the sex-specific prevalence, longitudinal changes of LV remodelling, and diastolic dysfunction in patients with T2DM. Further, the prognostic value of diastolic function in women and men was also evaluated. Methods and results  A total of 350 patients with T2DM (mean age 61 ± 11 years; women, 48.3%) was recruited. Detailed echocardiography was performed at baseline and after 25 months. A major adverse cardiovascular event (MACE) was defined as cardiovascular death, heart failure hospitalization, or myocardial infarction. Despite a similar age, prevalence of hypertension and body mass index, women had a higher prevalence of LV hypertrophy and diastolic dysfunction at baseline and follow-up compared with men. A total of 21 patients developed MACE (5 cardiovascular death, 9 hospitalization for heart failure, and 7 myocardial infarction) during a median follow-up of 56 months. Women with diastolic dysfunction had a higher incidence of MACE than those with normal diastolic function but this association was neutral in men. Multivariable Cox-regression analysis indicated that diastolic dysfunction was associated with MACE in women [hazard ratio = 6.30; 95% confidence interval (CI) = 1.06–37.54; P < 0.05] but not men (hazard ratio = 2.29, 95% CI = 0.67–7.89; P = 0.19). Conclusion  LV hypertrophy and diastolic dysfunction, both at baseline and follow-up, were more common in women than men. Pre-clinical diastolic dysfunction was independently associated with MACE only in women with T2DM but was neutral in men.


2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Shih-Chieh Shao ◽  
Kai-Cheng Chang ◽  
Ming-Jui Hung ◽  
Ning-I Yang ◽  
Yuk-Ying Chan ◽  
...  

Abstract Background To compare the cardiovascular event risk in type 2 diabetes patients newly receiving dapagliflozin vs. empagliflozin. Methods We conducted a retrospective cohort study by analyzing a multi-institutional electronic medical records database (Chang Gung Research Database) in Taiwan and included adult type 2 diabetes patients who were newly receiving sodium–glucose co-transporter 2 (SGLT2) inhibitors from 2016 to 2017. The primary outcome was a composite of cardiovascular death, myocardial infarction, ischemic stroke and heart failure. We followed up patients from initiation of SGLT2 inhibitors until the occurrence of cardiovascular events before December 31, 2018. We performed multivariable Cox proportional hazard modeling, adjusting for patients’ age, sex, laboratory data, co-morbidities, and concomitant medications. Results We identified 12,681 new SGLT2 inhibitor users with a mean age of 58.9 (SD 11.8) years, of whom 43.9% were female and 45.8% were new dapagliflozin users. A total of 10,442 person-years of dapagliflozin use and 12,096 person-years of empagliflozin use were included. Compared to empagliflozin users, new users of dapagliflozin were found to have similar risks for primary composite outcome (adjusted HR: 0.91; 95% CI 0.73–1.14), cardiovascular death (adjusted HR: 0.54; 95% CI 0.14–2.12), myocardial infarction (adjusted HR: 0.77, 95% CI 0.49–1.19) and ischemic stroke (adjusted HR: 1.15; 95% CI 0.80–1.65), but a lower risk of heart failure (adjusted HR: 0.68; 95% CI 0.49–0.95). Conclusion The risk of cardiovascular events was similar between dapagliflozin and empagliflozin new users, but dapagliflozin may have a better outcome in the reduction of heart failure in type 2 diabetes patients. Future prospective studies are required to confirm the findings.


Author(s):  
Miles Fisher

EMPA-REG OUTCOME was a landmark trial with the sodium-glucose co-transporter-2 (SGLT2) inhibitor empagliflozin, which demonstrated significant reductions in major adverse cardiovascular events (MACE, a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke) driven by reductions in cardiovascular deaths and accompanied by an early reduction in hospitalisation for heart failure. This was followed by cardiovascular outcome trials with canagliflozin, dapagliflozin and ertugliflozin. The CANVAS Program was an integrated analysis of the CANVAS and CANVAS-R trials with canagliflozin. It demonstrated a significant reduction in MACE, but not in any of the components, and there was an unexpected increase in amputations and fractures with canagliflozin. The DECLARE-TIMI 58 trial with dapagliflozin had two co-primary endpoints. A composite endpoint of cardiovascular death or hospitalisation for heart failure was significantly reduced, but there was no significant difference in MACE comparing dapagliflozin with placebo. Analysis of patients with a prior myocardial infarction, however, demonstrated significant reductions in MACE. The VERTIS CV trial with ertugliflozin was disappointing as there was no difference in MACE comparing ertugliflozin and placebo. In all four trials a reduction in hospitalisation for heart failure was observed in patients with type 2 diabetes, regardless of whether they had existing atherosclerotic cardiovascular disease or increased cardiovascular risk. Pre-specified renal outcomes were reduced with empagliflozin, canagliflozin and dapagliflozin, and these drugs are now commonly used in the management of people with type 2 diabetes. It is hard to envisage an ongoing role for ertugliflozin in routine clinical management as the evidence for its cardiovascular benefit is not convincing.


2021 ◽  
Vol 10 (Supplement_1) ◽  
Author(s):  
C Jackson-Pedroza ◽  
A Gallardo-Grajeda ◽  
C Dattoli-Alejo ◽  
R Gopar-Nieto ◽  
D Alfaro-Ponce ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf PHASE-MX Background/Introduction: Early routine angiography with subsequent Percutaneous Coronary Intervention (PCI) (if needed) after fibrinolysis reduced the rates of reinfarction and recurrent ischemia compared with a ‘watchful waiting’ strategy. A crucial issue is the optimal time delay between successful lysis and PCI, there is a wide variation in delay in trials from a median of 1.3 h to 17h (CAPITAL AMI, GRACIA-1 and STREAM trials). At present a time window of 2-24h after successful lysis is recommended. Purpose   To analyze the incidence of major cardiovascular outcomes in patients with ST-segment elevation myocardial infarction (STEMI) according to the timing of PCI after lysis (pharmacoinvasive strategy, less/more than 24h). Methods A retrospective analysis of the PHASE-MX study (ClinicalTrials.gov Identifier: NCT03974581) including patients with STEMI whom underwent pharmacoinvasive strategy during the first 12h since symptom onset. Patients were further stratified according to the time from the use of fibrinolysis to sheat insertion (<24h or >24h) in the completion of pharmacoinvasive strategy. The primary composite endpoint included the occurrence of cardiovascular death, cardiogenic shock, recurrent myocardial infarction or congestive heart failure at 30 days of follow-up. Results A total of 171 patients were included, of whom 34 underwent PCI after fibrinolysis in less than 24 hours and 137 underwent PCI in more than 24 hours (95% CI 24-120h). Mostly were male (86.4%), mean age was 56.4 ±12.1 years. The primary composite endpoint occurred in 2 patients (5.8%) in PCI < 24 hours and 12 patients (8.6%) in PCI >24 hours (p 0.58). PCI in <24h after lysis was not associated with a reduced risk of the primary endpoint (HR 0.66 95%CI: 0.14-2.97). Conclusion In patients with successful fibrinolysis undergoing to PCI the first 24 h was not associated with a reduced risk of cardiovascular death, cardiogenic shock, recurrent MI or congestive heart failure at 30 days comparing with PCI after 24 h. Abstract Figure. Kaplan-Meier in primary endpoint


2008 ◽  
Vol 42 (10) ◽  
pp. 1466-1474 ◽  
Author(s):  
Ujjaini Khanderia ◽  
Rodica Pop-Busui ◽  
Kim A Eagle

Objective: To examine the cardiovascular effects of thiazolidinediones (TZDs), discuss concerns regarding this drug class and its relation to heart failure (HF) and myocardial infarction (Ml), and address the clinical implications of HF and Ml. Data Sources: Literature was accessed through MEDLINE (1979-April 2008) using the search terms type 2 diabetes mellitus. thiazolidinediones. cardiovascular events, heart failure, myocardial infarction, and edema. Reviews, meta-analyses, clinical trials, observational studies (case-control, cohort), and descriptive studies (case reports, caso series) were included. Study Selection and Data Extraction: All articles that were written in English and identified from the data sources were reviewed. Data Synthesis: The American Diabetes Association recommends metformin as first-line therapy for type 2 diabetes, with the subsequent addition of a TZD, sulfonylurea, or insulin if the target is not met. Beyond glucose lowering, TZDs improvo various factors associated with cardiovascular risk. Whether the effects translate into beneficial cardiovascular outcomes is controversial. In PROactive (Prospective Pioglitazone Clinical Trial in Macrovascular Events), pioglitazone did not produce a significant reduction in the primary endpoint that included a composite of coronary and vascular deaths, but the secondary composite endpoint of all-cause mortality, Ml, or stroke was significantly reduced. Concerns related to HF have led to warnings in the labeling of TZDs. The drugs are contraindicated in patients with New York Head Association Class Ill or IV HF. Rosiglilazone, but not pioglitazone, is associated with an increased risk of myocardial ischemic events, although the absolute magnitude is extremely small. Conclusions: Although the glycemic efficacy of TZDs is comparable to that of metformin, ad verso effects and higher costs make TZDs less appealing for initial therapy. Among the TZDs. pioglitazone should be considered based on cardiovascular safety data. In combination with metformin, pioglitazone may be particularly beneficial for patients wilh diabetes and metabolic syndrome. For patients on rosigfitazone who are achieving glycemic goals and tolerating the therapy without apparent complications, rosiglitazone may be continued.


Cardiology ◽  
2021 ◽  
Author(s):  
Lucas Chun Wah Fong ◽  
Nicholas Ho Cheung Lee ◽  
Andrew T. Yan ◽  
Ming-Yen Ng

Introduction: There has been inconsistent data on the direct comparison of prasugrel and ticagrelor. This meta-analysis was conducted to summarise the current available evidence. Methods: We performed a meta-analysis (PROSPERO-registered CRD42020166810) of randomized trials up to Feb 2020 that compared prasugrel and ticagrelor in acute coronary syndrome with respect to the composite endpoint of myocardial infarction (MI), stroke or cardiovascular death, and secondary endpoints including MI, stroke, cardiovascular death, major bleeding (Bleeding Academic Research Consortium (BARC) type 2 or above), stent thrombosis, all-cause death and other safety outcomes. Results: Of the 11 eligible RCTs with 6098 patients randomized to prasugrel (n=3050) or ticagrelor (n=3048), 180 and 207 had the composite endpoint events in the prasugrel arm and the ticagrelor arm respectively over a weighted mean follow up period of 11±2 months. Compared with prasugrel, the ticagrelor group had similar risk in the primary composite endpoint (Risk Ratio (RR)= 1.17; 95% CI=0.96-1.42; p=0.12, I2=0%). Compared to prasugrel, there was no significant difference associated with the use of ticagrelor groups with respect to stroke (RR=1.05; 95% CI=0.66-1.67; p=0.84, I2=0%); cardiovascular death (RR=1.01; 95% CI=0.75-1.36; p=0.95, I2=0%); BARC type 2 or above bleeding (RR=1.16; 95% CI =0.89-1.52; p=0.26, I2=0%); stent thrombosis (RR=1.58; 95% CI =0.90-2.76; p=0.11, I2=0%); all cause death (RR=1.10; 95% CI =0.86-1.43; p=0.45, I2=0%) except MI (RR=1.38; 95% CI=1.05-1.81; p=0.02, I2=0%) Conclusion: Compared with prasugrel, ticagrelor did not reduce the primary composite endpoint of MI, stroke and cardiovascular death at a weighted mean follow up of 11 months. There was no significant difference between the secondary outcomes except myocardial infarction.


Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 588-P
Author(s):  
ANI S. TODOROVA ◽  
RUMYANA DIMOVA ◽  
NEVENA CHAKAROVA ◽  
MINA SERDAROVA ◽  
GRETA GROZEVA-DAMYANOVA ◽  
...  

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L.C.W Fong ◽  
N Lee ◽  
A.T Yan ◽  
M.Y Ng

Abstract Background Prasugrel and ticagrelor are both effective anti-platelet drugs for patients with acute coronary syndrome. However, there has been limited data on the direct comparison of prasugrel and ticagrelor until the recent ISAR-REACT 5 trial. Purpose To compare the efficacy of prasugrel and ticagrelor in patients with acute coronary syndrome with respect to the primary composite endpoint of myocardial infarction (MI), stroke or cardiac cardiovascular death, and secondary endpoints including MI, stroke, cardiovascular death, major bleeding (Bleeding Academic Research Consortium (BARC) type 2 or above), and stent thrombosis within 1 year. Methods Meta-analysis was performed on randomised controlled trials (RCT) up to December 2019 that randomised patients with acute coronary syndrome to either prasugrel or ticagrelor. RCTs were identified from Medline, Embase and ClinicalTrials.gov using Cochrane library CENTRAL by 2 independent reviewers with “prasugrel” and “ticagrelor” as search terms. Effect estimates with confidence intervals were generated using the random effects model by extracting outcome data from the RCTs to compare the primary and secondary clinical outcomes. Cochrane risk-of-bias tool for randomised trials (Ver 2.0) was used for assessment of all eligible RCTs. Results 411 reports were screened, and we identified 11 eligible RCTs with 6098 patients randomised to prasugrel (n=3050) or ticagrelor (n=3048). The included trials had a follow up period ranging from 1 day to 1 year. 330 events on the prasugrel arm and 408 events on the ticagrelor arm were recorded. There were some concerns over the integrity of allocation concealment over 7 trials otherwise risk of other bias was minimal. Patients had a mean age of 61±4 (76% male; 50% with ST elevation MI; 35% with non-ST elevation MI; 15% with unstable angina; 25% with diabetes mellitus; 64% with hypertension; 51% with hyperlipidaemia; 42% smokers). There was no significant difference in risk between the prasugrel group and the ticagrelor group on the primary composite endpoint (Figure 1) (Risk Ratio (RR)=1.17; 95% CI=0.97–1.41; p=0.10, I2=0%). There was no significant difference between the use of prasugrel and ticagrelor with respect to MI (RR=1.24; 95% CI=0.81–1.90; p=0.31); stroke (RR=1.05; 95% CI=0.66–1.67; p=0.84); cardiovascular death (RR=1.01; 95% CI=0.75–1.36; p=0.95); BARC type 2 or above bleeding (RR=1.17; 95% CI =0.90–1.54; p=0.24); stent thrombosis (RR=1.58; 95% CI =0.90–2.76; p=0.11). Conclusion Compared with ticagrelor, prasugrel did not reduce the primary composite endpoint of MI, stroke and cardiovascular death within 1 year. There was also no significant difference in the risk of MI, stroke, cardiovascular death, major bleeding and stent thrombosis respectively. Figure 1. Primary Objective Funding Acknowledgement Type of funding source: None


Author(s):  
Ani S. Todorova ◽  
Edward B. Jude ◽  
Rumyana B. Dimova ◽  
Nevena Y. Chakarova ◽  
Mina S. Serdarova ◽  
...  

The aim of this study was to assess vitamin D status in patients with type 2 diabetes and diabetic foot ulcers (DFU). A total of 242 participants with type 2 diabetes, mean age 59.1 ± 10 years, mean body mass index 31.4 ± 6.3 kg/m2, and estimated glomerular filtration rate ≥45 mL/min/1.73m2, were divided into 2 groups: 73 with DFU (35 with and 38 without active infection) and 169 without DFU (106 with diabetic peripheral neuropathy, 63 without complications). Neuropathy was assessed by 10 g monofilament, Rydel-Seiffer 128 Hz tuning fork, and temperature discrimination. Serum 25(OH)D (25-hydroxy vitamin D) was assessed by ECLIA (electro-chemiluminescence immunoassay) method. Median 25(OH)D level was 12.6 ng/mL (IQR [interquartile range] 9.3-17.6 ng/mL) in the studied cohort. The DFU group presented with lower 25(OH)D level as compared with diabetic patients without foot ulcers (non-DFU group): 11.6 ng/mL (IQR 8.5-15.8 ng/mL) versus 13.5 ng/mL (IQR 9.6-18.6 ng/mL), P = .001; the diabetic peripheral neuropathy subgroup demonstrated lower 25(OH)D level in comparison with participants without complications: 12.5 ng/mL (IQR 9-17.2 ng/mL) versus 15.9 ng/mL (IQR 10.4-20.8 ng/mL), P = .031. This remained significantly different even after correction for age and duration of diabetes. There was no difference in 25(OH)D level between the subgroups according to the presence of active infection. In conclusion, vitamin D deficiency may play a role in the development of diabetes complications.


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