Major Cardiovascular Outcomes Research Articles

Legacy effect of fibrate add-on therapy in diabetic patients with dyslipidemia: a secondary analysis of the ACCORDION study

BackgroundThe Action to Control Cardiovascular Risk in Diabetes (ACCORD)-Lipid study found no evidence of a beneficial effect of statin-fibrate combined treatment, compared to statins alone, on cardiovascular outcomes and mortality in type 2 diabetes mellitus after 5 years of active treatment. However, a beneficial reduction in major CVD events was shown in a pre-specified sub-group of participants with dyslipidemia. The extended follow-up of this trial provides the opportunity to further investigate possible beneficial effects of fibrates in this group of patients. We aimed to evaluate possible “legacy effects” of fibrate add-on therapy on mortality and major cardiovascular outcomes in patients with dyslipidemia.MethodsThe ACCORD-lipid study was a randomized controlled trial of 5518 participants assigned to receive simvastatin plus fenofibrate vs simvastatin plus placebo. After randomized treatment allocation had finished at the end of the trial, all surviving participants were invited to attend an extended follow-up study (ACCORDION) to continue prospective collection of clinical outcomes. We undertook a secondary analysis of trial and post-trial data in patients who had dyslipidemia. The primary outcome was all-cause and cardiovascular mortality, and secondary outcomes were nonfatal myocardial infarction, stroke, congestive heart failure and major coronary heart disease. We used an intention-to-treat approach to analysis to make comparisons between the original randomized treatment groups.Results853 participants with dyslipidemia had survived at the end of the trial. Most participants continued to use statins, but few used fibrates in either group during the post-trial period. The incidence rates in the fenofibrate group were lower with respect to all-cause mortality, CVD mortality, nonfatal myocardial infarction, congestive heart failure and major coronary heart disease than those in the placebo group over a post-trial follow-up. Allocation to the combined fibrate-statin treatment arm during the trial period had a beneficial legacy effect on all-cause mortality (adjusted HR = 0.65, 95% CI 0.45–0.94; P = 0.02).ConclusionsFibrate treatment during the initial trial period was associated with a legacy benefit of improved survival over a post-trial follow-up. These findings support re-evaluation of fibrates as an add-on strategy to statins in order to reduce cardiovascular risk in diabetic patients with dyslipidemia.Trial registration clinicaltrials.gov, Identifier: NCT00000620

Effects of Liraglutide on Cardiovascular Outcomes in Patients With Diabetes With or Without Heart Failure

BackgroundMore data regarding effects of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes (T2D) and heart failure (HF) are required. ObjectivesThe purpose of this study was to investigate the effects of liraglutide on cardiovascular events and mortality in LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) participants, by HF history. MethodsIn the multinational, double-blind, randomized LEADER trial, 9,340 patients with T2D and high cardiovascular risk were assigned 1:1 to liraglutide (1.8 mg daily or maximum tolerated dose up to 1.8 mg daily) or placebo plus standard care, and followed for 3.5 to 5 years. New York Heart Association (NYHA) functional class IV HF was an exclusion criterion. The primary composite major adverse cardiovascular events outcome was time to first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Post hoc Cox regression analyses of outcomes by baseline HF history were conducted. ResultsAt baseline, 18% of patients had a history of NYHA functional class I to III HF (liraglutide: n = 835 of 4,668; placebo: n = 832 of 4,672). Effects of liraglutide versus placebo on major adverse cardiovascular events were consistent in patients with (hazard ratio [HR]: 0.81 [95% confidence interval (CI): 0.65 to 1.02]) and without (HR: 0.88 [95% CI: 0.78 to 1.00]) a history of HF (p interaction = 0.53). In both subgroups, fewer deaths were observed with liraglutide (HR: 0.89 [95% CI: 0.70 to 1.14] with HF; HR: 0.83 [95% CI: 0.70 to 0.97] without HF; p interaction = 0.63) versus placebo. No increased risk of HF hospitalization was observed with liraglutide, regardless of HF history (HR: 0.98 [95% CI: 0.75 to 1.28] with HF; HR: 0.78 [95% CI: 0.61 to 1.00] without HF; p interaction = 0.22). Effects of liraglutide on the composite of HF hospitalization or cardiovascular death were consistent in patients with (HR: 0.92 [95% CI: 0.74 to 1.15]) and without (HR: 0.77 [95% CI: 0.65 to 0.91]) a history of HF (p interaction = 0.19). ConclusionsBased on these findings, liraglutide should be considered suitable for patients with T2D with or without a history of NYHA functional class I to III HF. (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results [LEADER]; NCT01179048)

A PROSPECTIVE STUDY OF HAND-GRIP STRENGTH AND OUTCOMES IN A CARDIOVASCULAR INTENSIVE CARE UNIT

Handgrip strength (HGS) is a marker of frailty that is associated with major adverse cardiovascular outcomes. The relationship between HGS and outcomes in a cardiovascular intensive care unit (CVICU) setting has not been previously studied. Between December 2018 and May 2019 HGS was measured on

META-ANALYSIS OF SAFETY AND EFFICACY OF BEMPEDOIC ACID

Safety and cardiovascular effectiveness of bempedoic acid remains uncertain. Ten randomized control trials were selected using Pubmed and Embase through October 2019. The clinical endpoints included major adverse cardiovascular outcomes (MACE), serious adverse events, muscle related adverse events

Metformin and cardiorenal outcomes in diabetes: A reappraisal.

The guidance issued to the pharmaceutical industry by the US Food and Drug Administration in 2008 has led to the publication of a series of randomized, controlled cardiovascular outcomes trials with newer therapeutic classes of glucose‐lowering medications. Several of these trials, which evaluated the newer therapeutic classes of sodium‐glucose co‐transporter‐2 inhibitors and glucagon‐like peptide‐1 receptor agonists, have reported a reduced incidence of major adverse cardiovascular and/or renal outcomes, usually relative to placebo and standard of care. Metformin was the first glucose‐lowering agent reported to improve cardiovascular outcomes in the UK Prospective Diabetes Study (UKPDS) and thus became the foundation of standard care. However, as this clinical trial reported more than 20 years ago, differences from current standards of trial design and evaluation complicate comparison of the cardiovascular profiles of older and newer agents. Our article revisits the evidence for cardiovascular protection with metformin and reviews its effects on the kidney.

The role of resting myocardial blood flow and myocardial blood flow reserve as a predictor of major adverse cardiovascular outcomes.

Cardiac perfusion PET is increasingly used to assess ischemia and cardiovascular risk and can also provide quantitative myocardial blood flow (MBF) and flow reserve (MBFR) values. These have been shown to be prognostic biomarkers of adverse outcomes, yet MBF and MBFR quantification remains underutilized in clinical settings. We compare MBFR to traditional cardiovascular risk factors in a large and diverse clinical population (60% African-American, 35.3% Caucasian) to rank its relative contribution to cardiovascular outcomes. Major adverse cardiovascular events (MACE), including unstable angina, non-ST and ST-elevation myocardial infarction, stroke, and death, were assessed for consecutive patients who underwent rest-dipyridamole stress 82Rb PET cardiac imaging from 2012–2015 at the Hospital of the University of Pennsylvania (n = 1283, mean follow-up 2.3 years). Resting MBF (1.1 ± 0.4 ml/min/g) was associated with adverse cardiovascular outcomes. MBFR (2.1 ± 0.8) was independently and inversely associated with MACE. Furthermore, MBFR was more strongly associated with MACE than both traditional cardiovascular risk factors and the presence of perfusion defects in regression analysis. Decision tree analysis identified MBFR as superior to established cardiovascular risk factors in predicting outcomes. Incorporating resting MBF and MBFR in CAD assessment may improve clinical decision making.

LDL-cholesterol lowering with evolocumab, and outcomes according to age and sex in patients in the FOURIER Trial.

Some trials have reported diminished efficacy for statins in the elderly, and in women compared with men. We examined the efficacy and safety of evolocumab by patient age and sex in the FOURIER trial, the first major cardiovascular outcome trial of a PCSK9 inhibitor. FOURIER was a randomised, double blind trial, comparing evolocumab with placebo in 27,564 patients with atherosclerotic cardiovascular disease receiving statin therapy (median follow-up 2.2 years). The primary endpoint was cardiovascular death, myocardial infarction, stroke, hospitalisation for unstable angina or coronary revascularisation. Cox proportional hazards models were used to assess the efficacy of evolocumab versus placebo stratified by quartiles of patient age and by sex. There were small variations in the cardiovascular event rate across the age range (for the primary endpoint, Kaplan-Meier at 3 years 15.6%, >69 years, vs. 15.1%, ≤56 years, P = 0.45); however, the relative efficacy of evolocumab was consistent regardless of patient age (for the primary endpoint (Q1 hazard ratio, 95% confidence interval) 0.83, 0.72-0.96, Q2 0.88, 0.76-1.01, Q3 0.82, 0.71-0.95, Q4 0.86, 0.74-1.00; Pinteraction = 0.91), and the key secondary endpoint (cardiovascular death, myocardial infarction, stroke) (Q1 0.74 (0.61-0.89), Q2 0.83 (0.69-1.00), Q3 0.78 (0.65-0.94), Q4 0.82 (0.69-0.98)); Pinteraction = 0.81). Women had a lower primary endpoint rate than men (Kaplan-Meier at 3 years 12.5 vs. 15.3%, respectively, P < 0.001). Relative risk reductions in the primary endpoint and key secondary endpoint were similar in women (0.81 (0.69-0.95) and 0.74 (0.61-0.90), respectively) compared with men (0.86 (0.80-0.94) and 0.81 (0.73-0.90), respectively), Pinteraction = 0.48 and 0.44, respectively. Adverse events were more common in women and with increasing age but, with the exception of injection site reactions, there were no important significant differences reported by those assigned evolocumab versus placebo. The efficacy and safety of evolocumab are similar throughout a broad range of ages and in both men and women.

Sleep duration and risk of cardiovascular events: The SAVE study.

Controversy exists regarding cardiovascular risk in relation to sleep duration. We determined sleep duration and major recurrent cardiovascular event associations in patients with obstructive sleep apnoea and established cardiovascular disease. Secondary analyses of the international, multicenter, Sleep Apnea Cardiovascular Endpoints trial. Sleep duration was estimated from overnight home oximetry (ApneaLink monitor) used for obstructive sleep apnoea diagnosis. Cox proportional hazards models were used to determine associations of categorized sleep duration (<6 h, 6-8 h (reference), and >8 h) and major cardiovascular outcomes: primary composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and any hospitalization for unstable angina, heart failure, or transient ischemic attack; secondary composite of cardiac and cerebral (stroke/transient ischemic attack) events. Oximetry-derived sleep duration estimates were available in 2687 participants (mean 61.2 years, 80.9% males) who experienced a total of 436 cardiovascular events over a mean follow-up of 3.7 years. Compared to the reference category, sleep duration was not associated with risk of the primary composite cardiovascular outcome (adjusted hazard ratio (HR) 1.00, 95% confidence interval 0.76-1.33, and HR 1.22, 95% confidence interval 0.98-1.52, for sleep duration <6 and >8 h, respectively). However, long sleep was associated with increased cerebral events (HR 1.67, 95% confidence interval 1.17-2.39; P = 0.005) and stroke alone (HR 1.79, 95% confidence interval 1.22-2.63; P = 0.003). Long sleep duration is associated with an increased risk of stroke but not cardiac events in obstructive sleep apnoea patients with existing cardiovascular disease. The trial is registered at ClinicalTrials.gov (NCT00738179).

Impact of Side-Branch Predilation on Angiographic Outcomes in Non-Left Main Coronary Bifurcation Lesions.

Despite the high prevalence of coronary bifurcation lesions in routine interventional cardiology practice, the best strategy for managing this challenging lesion subset remains debatable. Due to potential for complications, the routine practice of side-branch (SB) predilation is controversial. An electronic search was performed of online databases up until April 2018 for studies reporting periprocedural angiographic outcomes comparing provisional main-branch stenting with and without SB predilation. Random-effects model odds ratios (ORs) were calculated. Eight studies were selected for a qualitative review, with 47.3% (1367/2890) of included subjects having angiographic outcomes following SB predilation reported. Of these, four studies included details of periangiographic outcomes comparing two groups. Bifurcation lesions stented without SB predilation demonstrated lower odds of requiring further SB intervention compared with lesions receiving upfront SB predilation (OR, 2.44; 95% confidence interval [CI], 1.71-3.47; I²=21%; P<.001). No difference was demonstrated regarding final SB TIMI flow <3, SB dissection, or intraprocedural SB occlusion. Although the odds of performing final kissing-balloon inflation were in favor of the group without SB predilation (OR, 1.62; 95% CI, 1.11-2.37; I²=61%; P=.01), there was no statistical difference in long-term major cardiovascular outcome (MACE) between the two groups (risk ratio, 1.29; 95% CI, 0.94-1.75; I²=11%; P=.33). SB predilation during coronary bifurcation percutaneous coronary intervention did not alter overall procedural angiographic outcomes. However, SB predilation is associated with increased SB intervention, including increased requirement for SB stenting, without demonstrable long-term MACE benefit, compared with a standard strategy without SB predilation.

Outcomes of Chronic Total Occlusion Percutaneous Coronary Intervention in Patients With Renal Dysfunction

Although contemporary chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is performed with high success rates, 10% to 13% of patients presenting with CTOs have chronic kidney disease (CKD), and the comparative safety, efficacy, and health status benefit of CTO PCI in these patients, has not been well defined. We examined the association of baseline renal function with periprocedural major adverse cardiovascular and cerebral events and health status outcomes in 957 consecutive patients (mean age 65.3 ± 10.3 years, 19.4% women, 90.3% white, 23.6 CKD [estimated glomerular filtration rate {eGFR} < 60]) in the OPEN-CTO (Outcomes, Patients Health Status, and Efficiency in Chronic Total Occlusions Registry) study. Hierarchical multivariable regression models were used to examine the independent association of baseline eGFR with technical success, periprocedural complications and change in health status, using Seattle Angina Questionnaire (SAQ) over 1 year. Crude rates of acute kidney injury were higher (13.5% vs 4.4%, p <0.001) and technical success lower (81.8% vs 88.4%, p = 0.01) in patients with CKD. There were no significant differences in other periprocedural complications. After adjustment for confounding factors, there was no significant association of baseline eGFR with technical success or periprocedural major adverse cardiovascular and cerebral events (death, myocardial infarction, emergent bypass surgery, stroke, perforation), whereas patients with lower eGFR had higher rates of acute kidney injury. The difference in SAQ summary score, between patients on the 10th and 90th percentile for baseline eGFR distribution was not clinically significant (1 month: -0.91; 1 year: -3.06 points). In conclusion, CTO PCI success, complication rates, and the health status improvement after CTO PCI are similar in patients across a range of baseline eGFRs.

459 CMV Antibody Level is an Independent Risk Factor for MACCE and Death in the General Population

Cytomegalovirus (CMV) infections have been linked to increased cardiovascular disease burden in healthy adults. Previous studies have considered CMV serostatus and not antibody levels, which tend to increase with age and may reflect reactivations of latent CMV. We investigated the association between CMV antibody levels and all-cause death and major cardiovascular outcomes in a community-based cohort. CMV antibody levels were determined using an in-house enzyme-linked immunosorbent assay in stored plasma samples from 825 participants aged 58-79 years from the 1994/95 Busselton Health Study cohort with no history of cardiovascular disease. Cox regression models were used to determine the adjusted hazard ratios for CMV antibody levels as continuous predictor of all-cause death and MACCE (composite of all-cause death, acute coronary syndrome, coronary artery revascularisation procedures or ischaemic stroke) at 5 and 20 years follow-up, adjusting for conventional risk factors. Of the 825 participants, 638 (77.3%) were CMV seropositive. In the fully adjusted model, higher CMV antibody levels were associated with an increased risk of all-cause death at 5 years (HR 1.26 per 1 standard deviation (SD) increase in CMV antibody level, 95% CI 1.02-1.55) and 20 years (HR 1.12, 95% CI 1.01-1.24) follow-up. Furthermore, higher levels of CMV antibody were associated with an increased risk of MACCE at 5 years (HR 1.21 per 1 SD increase in CMV antibody, 95% CI 1.01-1.44) and 20 years (HR 1.13, 95% CI 1.03-1.24) follow-up. CMV antibody levels are independently associated with risk of death and MACCE in the general population.

HIGH ADMISSION PLASMA OSMOLALITY VALUE AS IN-HOSPITAL MAJOR ADVERSE CARDIOVASCULAR EVENTS PREDICTOR IN PATIENT WITH ACUTE MYOCARDIAL INFARCTION

Background: Elevated blood urea nitrogen (BUN), blood glucose, and alteration sodium levels are common among patients with acute myocardial infarction (AMI). These parameters to be widely investigated to assess the prognosis in AMI patients. However, the combination of these parameters (BUN, blood glucose, and sodium) calculated by a certain formula in the form of plasma osmolality has not been widely studied to assess the prognosis of patients with acute myocardial infarction. This study aims to assess plasma osmolality in predicting hospital major adverse cardiovascular events (MACEs) among AMI patients. Methods: Data were collected from 118 consecutive patients with AMI in Cardiac Centre Haji Adam Malik General Hospital Medan. We measured admission plasma osmolality [1,86 (Na+) + BUN/2,8 + Glucose/18+9]. Then we observed in hospital Major Adverse Cardiovascular Outcomes (MACEs) which consist of cardiovascular mortality, acute heart failure, malignant arrhythmia, and cardiogenic shock. Statistical analysis was performed using mean difference, logistic regression, and receiver operating curve (ROC). Result: Among 118 patients, MACEs were observed in 49 (41.5%) patients with the most common MACEs was acute heart failure (25.4%). Bivariate analysis showed a significant relationship between the plasma osmolality and in hospital MACEs (p &lt; 0.001). The plasma osmolality AUC prediction value was 78.9%. The optimal cut-off value was 279.9 mOsm/kg (sensitivity 81.6%; specificity 75.4%). In multivariate logistic regression analysis, the plasma osmolality was the strongest predictor with an OR value of 10.542 (95% CI 2.694-41.255; p-value &lt;0.001). Conclusions: Among AMI patients, high plasma osmolality value (≥280 mOsm/kg) is a better predictor of in-hospital MACEs than its components separately(BUN, glucose level, sodium).

Have the Major Cardiovascular Outcomes Trials Impacted Payer Approval Rates for PCSK9 Inhibitors?

Have the Major Cardiovascular Outcomes Trials Impacted Payer Approval Rates for PCSK9 Inhibitors?

Comparison of Long-Term Outcomes of Patients Having Surgical Aortic Valve Replacement With Versus Without Simultaneous Coronary Artery Bypass Grafting

Coronary artery disease is a common co-morbidity of aortic stenosis. When needed, adding coronary artery bypass grafting (CABG) to surgical aortic valve replacement (SAVR) is the standard treatment method, but the impact of concomitant CABG on long-term outcomes is uncertain. We compared long-term outcomes of SAVR patients with and without CABG. Hospital survivors aged ≥50 years discharged after SAVR ± CABG in Finland between 2004 and 2014 (n = 6,870) were retrospectively studied using nationwide registries. Propensity score matching (1:1) was used to identify patients with comparable baseline features (n = 2,188 patient pairs, mean age 73 years). The end points were postoperative 10-year major adverse cardiovascular outcome (MACE), all-cause mortality, stroke, major bleeding, and myocardial infarction. Median follow-up was 6 years. Cumulative MACE rate (39.5% vs 35.6%; hazard ratio [HR] 1.04; p = 0.677) and mortality (32.7% vs 31.0%; HR 1.03; p = 0.729) after SAVR were comparable with or without CABG. Myocardial infarction was more common in patients with CABG (13.4% vs 6.9%; HR 1.47; p = 0.0495). Occurrence of stroke (15.1% vs 13.5%; p = 0.998) and major bleeding (20.0% vs 21.9%; p = 0.569) were comparable. There was no difference in gastrointestinal (8.1% vs 10.3%; p = 0.978) or intracranial bleeds (6.0% vs 5.5%; p = 0.794). The use of internal mammary artery in CABG did not have an impact on the results. In conclusion, matched patients with and without concomitant CABG had comparable long-term MACE, mortality, stroke, and major bleeding rates after SAVR. In conclusion, our results indicate that need for concomitant CABG has limited impact on long-term outcomes after initially successful SAVR.

Timing of Staged Nonculprit Artery Revascularization in Patients With ST-Segment Elevation Myocardial Infarction: COMPLETE Trial

BackgroundThe COMPLETE (Complete vs Culprit-only Revascularization to Treat Multi-vessel Disease After Early PCI for STEMI) trial demonstrated that staged nonculprit lesion percutaneous coronary intervention (PCI) reduced major cardiovascular (CV) events in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (CAD). ObjectivesThe purpose of this study was to determine the effect of nonculprit-lesion PCI timing on major CV outcomes and also the time course of the benefit of complete revascularization. MethodsFollowing culprit-lesion PCI, 4,041 patients with STEMI and multivessel CAD were randomized to staged nonculprit-lesion PCI or culprit-lesion only PCI. Randomization was stratified according to investigator-planned timing of nonculprit-lesion PCI: during or after the index hospitalization. The first coprimary outcome was the composite of CV death or myocardial infarction (MI). In pre-specified analyses, hazard ratios (HRs) were calculated for each time stratum. Landmark analyses of the entire population were performed within 45 days and after 45 days. ResultsFor nonculprit-lesion PCI planned during the index hospitalization (actual time: median 1 day), CV death or MI was reduced with complete revascularization compared with culprit-lesion only PCI (HR: 0.77; 95% confidence interval [CI]: 0.59 to 1.00). For nonculprit lesion PCI planned to occur after hospital discharge (actual time: median 23 days), CV death or MI was also reduced with complete revascularization (HR: 0.69; 95% CI: 0.49 to 0.97; interaction p = 0.62). Landmark analyses demonstrated an HR of 0.86 (95% CI: 0.59 to 1.24) during the first 45 days and 0.69 (95% CI: 0.54 to 0.89) from 45 days to the end of follow-up for intended nonculprit lesion PCI versus culprit lesion only PCI. ConclusionsAmong STEMI patients with multivessel disease, the benefit of complete revascularization over culprit-lesion only PCI was consistent irrespective of the investigator-determined timing of nonculprit-lesion intervention. The benefit of complete revascularization on hard clinical outcomes emerged mainly over the long term.

Comparison of Cardiovascular Risk Factors and Outcomes Among Practicing Physicians vs the General Population in Ontario, Canada

Although cardiovascular disease is the leading cause of death in most developed countries, little is known about current physicians' cardiovascular health and outcomes. To compare cardiac risk factor burden, health services use, and major cardiovascular event incidence between physicians and the general population. This cohort study used data from practicing physicians and nonphysicians without cardiovascular disease aged 40 to 75 years in Ontario, Canada. Cohorts were assembled beginning January 1, 2008, and were followed up to December 31, 2015. Data analysis was performed between November 2017 and September 2019. Being a practicing physician. The primary outcome was 8-year incidence of a major cardiovascular event (ie, cardiovascular death or hospitalization for myocardial infarction, stroke, heart failure, or coronary revascularization). Secondary outcomes included health services used, such as physician assessments and guideline-recommended tests. The cohort comprised 17 071 physicians (mean [SD] age, 53.3 [8.8] years; 11 963 [70.1%] men) and 5 306 038 nonphysicians (mean [SD] age, 53.7 [9.5] years; 2 556 044 [48.2%] men). Physicians had significantly lower baseline rates of hypertension (16.9% vs 29.6%), diabetes (5.0% vs 11.3%), and smoking (13.1% vs 21.6%), while having better cholesterol profiles (total cholesterol levels >240 mg/dL, 13.3% vs 16.5%; low-density lipoprotein cholesterol >130 mg/dL, 33.2% vs 36.8%); age- and sex-adjusted differences were even larger. Physicians also had lower rates of periodic health examinations (58.9% [95% CI, 57.5%-60.4%] vs 67.9% [95% CI, 67.8%-67.9%]), hyperlipidemia screening (76.3% [95% CI, 74.7%-78.0%] vs 83.8% [95% CI, 83.7%-83.9%]), and diabetes screening (79.0% [95% CI, 77.3%-80.8%] vs 85.3% [95% CI, 85.2%-85.4%]), but higher rates of cardiologist consultations (25.2% [95% CI, 24.2%-26.3%] vs 19.5% [95% CI, 19.4%-19.5%]). The 8-year age- and sex-standardized primary outcome incidence was 4.4 major cardiovascular events per 1000 person-years for physicians and 7.1 major cardiovascular events per 1000 person-years for the general population. After adjusting for age, sex, socioeconomic status, and cardiac risks and comorbidities, physicians had a 22% lower hazard (hazard ratio, 0.78; 95% CI, 0.72-0.85) of experiencing the primary outcome compared with the general population. Practicing physicians in Ontario had fewer cardiovascular risk factors, underwent less preventive testing, and were less likely to experience major adverse cardiovascular outcomes than the general population.

Patients With Atrial Fibrillation Taking Nonsteroidal Anti-Inflammatory Drugs and Oral Anticoagulants in the ARISTOTLE Trial.

The use of nonsteroidal anti-inflammatory drugs (NSAIDs) with oral anticoagulants has been associated with an increased risk of bleeding. We investigated the risk of bleeding and major cardiovascular outcomes in patients with atrial fibrillation taking NSAIDs and apixaban or warfarin. The ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; n=18 201) compared apixaban with warfarin in patients with atrial fibrillation at an increased risk of stroke. Patients in ARISTOTLE without severe renal (creatine clearance ≤30 mL/min) or liver disease were included in this analysis (n=17 423). NSAID use at baseline, NSAID use during the trial (incident NSAID use), and never users were described. The primary outcome was major bleeding. Secondary outcomes included clinically relevant nonmajor bleeding, gastrointestinal bleeding, heart failure hospitalization, stroke or systemic embolism, and all-cause mortality. NSAID use during the trial, and the interaction between randomized treatment, was analyzed using time-dependent Cox proportional hazards models. Those with baseline NSAID use (n=832 [4.8%]), incident NSAID use (n=2185 [13.2%]), and never users were similar in median age (age [25th, 75th]; 70 [64, 77] versus 70 [63, 75] versus 70 [62, 76]). Those with NSAID use at baseline and incident NSAID use were more likely to have a history of bleeding than never users (24.5% versus 21.0% versus 15.6%, respectively). During a median follow-up (25th, 75th) of 1.8 (1.4, 2.3) years and when excluding those taking NSAID at baseline, we found that incident NSAID use was associated with an increased risk of major bleeding (hazard ratio [HR], 1.61 [95% CI, 1.11-2.33]) and clinically relevant nonmajor bleeding (HR, 1.70 [95% CI, 1.16-2.48]), but not gastrointestinal bleeding. No significant interaction was observed between NSAID use and randomized treatment for any outcome. A substantial number of patients in the ARISTOTLE trial took NSAIDs. Incident NSAID use was associated with major and clinically relevant nonmajor bleeding, but not with gastrointestinal bleeding. The safety and efficacy of apixaban versus warfarin appeared not significantly to be altered by NSAID use. This study warrants more investigation of the effect of NSAIDs on the outcomes of patients treated with apixaban. URL: https://www.clinicaltrials.gov. Unique identifier: NCT00412984.

Microvascular complications burden (nephropathy, retinopathy and peripheral polyneuropathy) affects risk of major vascular events and all-cause mortality in type 1 diabetes: a 10-year follow-up study

BackgroundMicrovascular complications (MC) have been claimed to increase the risk for cardiovascular disease in diabetic subjects. However, the effect of MC burden on the risk of major vascular outcomes and all-cause mortality in type 1 diabetes is still poorly explored. We evaluated the relationship between microvascular complications burden and incidence of major cardiovascular events and all-cause mortality in subjects with type 1 diabetes.MethodsWe recruited 774 participants with type 1 diabetes in a single-center observational study over a follow-up of 10.8 ± 2.5 years. Hazard ratios (HR) for cardiovascular outcomes and all-cause death associated with microvascular complications were determined by unadjusted and adjusted Cox regression analysis.ResultsOut of 774 individuals, 54.9% had no-MC, 32.3% 1 MC, 9.7% 2 MC and 3.1% 3 MC. A total of 54 deaths (7.0%) occurred. Death rate increased from no-MC 2.1% (Ref) to 1 MC 7.2% (HR 3.54 [95% CI 1.59–7.87]), 2 MC 14.7% (HR 6.41 [95% CI 2.65–15.49]) and 3 MC 66.7% (HR 41.73 [95% CI 18.42–94.57], p < 0.0001). After adjustments, HRs were: 1 MC 2.05 (95% CI 0.88–4.76), 2 MC 1.98 (95% CI 0.75–5.21), 3 MC 7.02 (95% CI 2.44–20.20, p = 0.002). Forty-nine subjects (6.7%) had at least one cardiovascular event, and cumulative incidence went from no-MC 2.2% (Ref) to 1 MC 5.0%; (HR 2.27 [95% CI 0.96–5.38]), 2 MC 26.8% (HR 12.88 [95% CI 5.82–28.50]) and 3 MC 40.9% (HR 29.34 [95% CI 11.59–74.25], p < 0.0001). Upon adjustments, HRs were: 1 MC 1.59 (95% CI 0.65–3.88), 2 MC 4.33 (95% CI 1.75–10.74), 3 MC 9.31 (95% CI 3.18–27.25, p < 0.0001). Thirty-five individuals (4.8%) had at least one coronary event, which cumulative incidence increased with MC burden (p < 0.0001).ConclusionsIn type 1 diabetes, microvascular complications burden increases in an independent dose-dependent manner the risk of major cardiovascular outcomes and all-cause mortality. The presence and number of microvascular complications should be considered in stratifying overall cardiovascular risk in type 1 diabetes.

Antioxidant, Anti-Inflammatory, and Metabolic Properties of Tocopherols and Tocotrienols: Clinical Implications for Vitamin E Supplementation in Diabetic Kidney Disease.

Diabetes mellitus is a metabolic disorder characterized by the development of vascular complications associated with high morbidity and mortality and the consequent relevant costs for the public health systems. Diabetic kidney disease is one of these complications that represent the main cause of end-stage renal disease in Western countries. Hyperglycemia, inflammation, and oxidative stress contribute to its physiopathology, and several investigations have been performed to evaluate the role of antioxidant supplementation as a complementary approach for the prevention and control of diabetes and associated disturbances. Vitamin E compounds, including different types of tocopherols and tocotrienols, have been considered as a treatment to tackle major cardiovascular outcomes in diabetic subjects, but often with conflicting or even negative results. However, their effects on diabetic nephropathy are even less clear, despite several intervention studies that showed the improvement of renal parameters after supplementation in patients with diabetic kidney disease. Then we performed a review of the literature about the role of vitamin E supplementation on diabetic nephropathy, also describing the underlying antioxidant, anti-inflammatory, and metabolic mechanisms to evaluate the possible use of tocopherols and tocotrienols in clinical practice.

Cardiovascular risk factors' behavior during the early stages of the disease, in Hispanic rheumatoid arthritis patients: a cohort study.

Rheumatoid arthritis (RA) patients from Latin America present distinctive characteristics relevant when assessing their cardiovascular (CV) risk. The objective was to monitor CV risk factor behavior in the early stages of the disease and to identify predictors of major CV outcomes (MACE). A recent-onset RA cohort was initiated in 2004; data from 185 patients with ≥ 1year of follow-up were analyzed. Patients underwent prospective assessments of CV risk factors. Incident MACE were confirmed according to standardized definitions. Appropriated statics was used based on the distribution of the variables. At baseline, patients were primarily middle-aged females (87.6%), with active disease (69.7%). Most prevalent CV risk factors were C-reactive-protein > 1mg/L (90.3%), Castelli ratio > 3 (83.8%), and low-high-density lipoprotein levels (73.5%). The number of patients with an incident CV risk factor after 1year was higher for a Castelli ratio > 3 (23%), low-high-density lipoprotein serum cholesterol (16.3%), high total serum cholesterol (10.6%), and BMI ≥ 30kg/m2 (10%). A minority of patients met the age-range criteria for the application of ACC/AHA 2013 criteria and Reynolds Risk Score (45.8% and 34.1%, respectively). Fifteen patients were classified with high-CV risk during the first year of follow-up, according to ACC/AHA 2013 criteria. Until June 2018, the cohort underwent 1358 patient/years follow-up; six patients developed incidental MACE; high-CV risk at baseline failed to predict MACE. Recent-onset RA Hispanic patients present a distinctive pattern and first-year behavior of CV risk factors. During follow-up, few patients developed incidental MACE.