EXERCISE-INDUCED VENTRICULAR ECTOPY AND FUTURE CARDIOVASCULAR DEATH IN ASYMPTOMATIC INDIVIDUALS: A 20-YEAR FOLLOW-UP OF THE LIPID RESEARCH CLINICS PREVALENCE STUDY

Introduction: Obese patients (BMI≥30 kg/m 2 ) with CAD have better outcomes as compared with non-obese patients, but the underlying pathobiology is unclear. Hypothesis: Obesity is directly associated with vascular regenerative capacity, measured as circulating progenitor cell (CPC) count, and this association provides insight into obesity paradox pathobiology. Methods: CPCs were enumerated by flow cytometry as CD45 med+ cells expressing CD34+, CD133+, and CXCR4+ epitopes in 672 asymptomatic individuals (50 y, 66% women, 23% Black, 28% obese) and 1,277 patients with CAD (66 y, 39% women, 22% Black, 39% obese). Association of obesity with CPC counts was analyzed using multivariable-adjusted linear regression models. Association of obesity and CPCs with cardiovascular death/myocardial infarction events over 3.5-y follow-up was studied using Kaplan-Meir survival curves and Cox models. Results: Obesity was independently associated with 16-34% higher CPC count (CD34+, CD34+/CD133+, and CD34+/CXCR4+) in asymptomatic individuals. This association was not attenuated after adjusting for measures of systemic inflammation, insulin resistance, or insulin secretion. Cardiorespiratory fitness and android fat only partly attenuated the obesity-CPC relationship. In patients with CAD, obesity was independently associated with 8-12% higher CPC counts, and with 30% lower outcome risk. Lower CPC counts were associated with outcome risk in obese patients. Obese patients with high CD34+ count (≥median) were at a lower risk, while obese participants with low counts (<median) were at a similar risk as compared with non-obese patients with high counts. The highest risk was observed in non-obese patients with low counts. Similar results were observed with CD34+/CD133+ and CD34+/CXCR4+ cells. Conclusions: Obesity is directly associated with vascular regenerative capacity, and the obesity paradox in CAD is observed in obese patients with high, but not low, CPC counts.

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Faculty Opinions recommendation of A 15-Year Warranty Period for Asymptomatic Individuals Without Coronary Artery Calcium: A Prospective Follow-Up of 9,715 Individuals.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725659319.793511343 ◽

2015 ◽

Author(s):

Sergio Fazio ◽

Michael D. Shapiro

Keyword(s):

Coronary Artery ◽

Coronary Artery Calcium ◽

Warranty Period ◽

Asymptomatic Individuals

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Cardiovascular consequences of discontinuing low-dose rivaroxaban in people with chronic coronary or peripheral artery disease

Heart ◽

10.1136/heartjnl-2020-318758 ◽

2021 ◽

pp. heartjnl-2020-318758

Author(s):

Gilles R Dagenais ◽

Leanne Dyal ◽

Jacqueline J Bosch ◽

Darryl P Leong ◽

Victor Aboyans ◽

...

Keyword(s):

Peripheral Artery Disease ◽

Low Dose ◽

Cardiovascular Death ◽

Stroke Rate ◽

Early Stopping ◽

Peripheral Artery ◽

Once Daily ◽

Registration Number ◽

Artery Disease

ObjectiveIn patients with chronic coronary or peripheral artery disease enrolled in the Cardiovascular Outcomes for People Using Anticoagulation Strategies trial, randomised antithrombotic treatments were stopped after a median follow-up of 23 months because of benefits of the combination of rivaroxaban 2.5 mg two times per day and aspirin 100 mg once daily compared with aspirin 100 mg once daily. We assessed the effect of switching to non-study aspirin at the time of early stopping.MethodsIncident composite of myocardial infarction, stroke or cardiovascular death was estimated per 100 person-years (py) during randomised treatment (n=18 278) and after study treatment discontinuation to non-study aspirin (n=14 068).ResultsDuring randomised treatment, the combination compared with aspirin reduced the composite (2.2 vs 2.9/100 py, HR: 0.76, 95% CI 0.66 to 0.86), stroke (0.5 vs 0.8/100 py, HR: 0.58, 95% CI 0.44 to 0.76) and cardiovascular death (0.9 vs 1.2/100 py, HR: 0.78, 95% CI 0.64 to 0.96). During 1.02 years after early stopping, participants originally randomised to the combination compared with those randomised to aspirin had similar rates of the composite (2.1 vs 2.0/100 py, HR: 1.08, 95% CI 0.84 to 1.39) and cardiovascular death (1.0 vs 0.8/100 py, HR: 1.26, 95% CI 0.85 to 1.86) but higher stroke rate (0.7 vs 0.4/100 py, HR: 1.74, 95% CI 1.05 to 2.87) including a significant increase in ischaemic stroke during the first 6 months after switching to non-study aspirin.ConclusionDiscontinuing study rivaroxaban and aspirin to non-study aspirin was associated with the loss of cardiovascular benefits and a stroke excess.Trial registration numberNCT01776424.

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Comparison of two recent ceramide-based coronary risk prediction scores: CERT and CERT-2

European Heart Journal ◽

10.1093/ehjci/ehaa946.2922 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Leiherer ◽

A Muendlein ◽

C.H Saely ◽

R Laaksonen ◽

M Laaperi ◽

...

Keyword(s):

Cardiovascular Mortality ◽

Coronary Event ◽

Cardiovascular Death ◽

Survival Models ◽

Risk Category ◽

Net Reclassification Improvement ◽

Event Risk ◽

Risk Predictor ◽

Risk Categories

Abstract The Coronary Event Risk Test (CERT) is a validated cardiovascular risk predictor that uses circulating ceramide concentrations to allocate patients into one of four risk categories. This test has recently been updated (CERT-2), now additionally including phosphatidylcholine concentrations. The purpose of this study was to investigate the power of CERT and CERT-2 to predict cardiovascular mortality in patients with cardiovascular disease (CVD). We investigated a cohort of 999 patients with established CVD. Overall, comparing survival curves (figure) for over 12 years of follow up and the predictive power of survival models using net reclassification improvement (NRI), CERT-2 was the best predictor of cardiovascular mortality, surpassing CERT (NRI=0.456; p=0.01) and also the 2019 ESC-SCORE (NRI=0.163; p=0.04). Patients in the highest risk category of CERT as compared to the lowest category had a HR of 3.63 [2.09–6.30] for cardiovascular death; for CERT-2 the corresponding HR was 6.02 [2.47–14.64]. Among patients with T2DM (n=322), the HR for cardiovascular death was 3.00 [1.44–6.23] using CERT and 7.06 [1.64–30.50] using CERT-2; the corresponding HRs among non-diabetic subjects were 2.99 [1.20–7.46] and 3.43 [1.03–11.43], respectively. We conclude that both, CERT and CERT-2 scores are powerful predictors of cardiovascular mortality in CVD patients, especially in those patients with T2D. Performance is even higher with CERT-2. Funding Acknowledgement Type of funding source: None

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The current treatment and predictors of outcome in elderly patients with non-ST-elevation myocardial infarction in an all comers population: the POPular Age registry

European Heart Journal ◽

10.1093/ehjci/ehaa946.3248 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M.E Gimbel ◽

D.R.P.P Chan Pin Yin ◽

R.S Hermanides ◽

F Kauer ◽

A.H Tavenier ◽

...

Keyword(s):

Myocardial Infarction ◽

Elderly Patients ◽

Major Bleeding ◽

Oral Anticoagulation ◽

Dual Antiplatelet Therapy ◽

Bleeding Risk ◽

Cardiovascular Death ◽

St Elevation ◽

One Year

Abstract Background Elderly patients form a large and growing part of the patients presenting with non-ST-elevation myocardial infarction (NSTEMI). Choosing the optimal antithrombotic treatment in these elderly patients is more complicated because they frequently have characteristics indicating both a high ischaemic and high bleeding risk. Purpose We describe the treatment of elderly patients (>75 years) admitted with NSTEMI, present the outcomes (major adverse cardiovascular events (MACE) and bleeding) and aim to find predictors for adverse events. Methods The POPular AGE registry is an investigator initiated, prospective, observational, multicentre study of patients aged 75 years or older presenting with NSTEMI. Patients were recruited between August 1st, 2016 and May 7th, 2018 at 21 sites in the Netherlands. The primary composite endpoint of MACE included cardiovascular death, non-fatal myocardial infarction and non-fatal stroke at one-year follow-up. Results A total of 757 patients were enrolled. During hospital stay 76% underwent coronary angiography, 34% percutaneous coronary intervention and 12% coronary artery bypass grafting (CABG). At discharge 78.6% received aspirin (non-users mostly because of the combination of oral anticoagulant and clopidogrel), 49.7% were treated with clopidogrel, 34.2% with ticagrelor and 29.6% were prescribed oral anticoagulation. Eighty-three percent of patients received dual antiplatelet therapy (DAPT) or dual therapy consisting of oral anticoagulation and at least one antiplatelet agent for a duration of 12 months. At one year, the primary outcome of cardiovascular death, myocardial infarction or stroke occurred in 12.3% of patients and major bleeding (BARC 3 or 5) occurred in 4.8% of the patients. The risk of MACE and major bleeding was highest during the first month and stayed high over time for MACE while the risk for major bleeding levelled off. Independent predictors for MACE were age, renal function, medical history of CABG, stroke and diabetes. The only independent predictor for major bleeding was haemoglobin level on admission. Conclusion In this all-comers registry, most elderly patients (≥75 years) with NSTEMI are treated with DAPT and undergoing coronary angiography the same way as younger NSTEMI patients from the SWEDEHEART registry. Aspirin use was lower as was the use of the more potent P2Y12 inhibitors compared to the SWEDEHEART which is very likely due to the concomitant use of oral anticoagulation in 30% of patients. The fact that ischemic risk stays constant over 1 year of follow-up, while the bleeding risk levels off after one month may suggest the need of dual antiplatelet therapy until at least one year after NSTEMI. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): AstraZeneca

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FRI0094 SIGNIFICANT IMPROVEMENT OF NT-PROBNP LEVELS IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH TOCILIZUMAB AND TOFACITINIB

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5859 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 625.2-626

Author(s):

H. Gerasimova ◽

T. Popkova ◽

I. Kirillova ◽

M. Cherkasova ◽

A. Martynova ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Cardiovascular Death ◽

Control Group ◽

Activity Levels ◽

Das 28 ◽

Interleukin 6 Receptor ◽

Inflammatory Drugs ◽

Roche Diagnostics

Background:N-terminal pro-brain natriuretic peptide (NT-proBNP) is a recognized predictor of congestive heart failure (CHF) and cardiovascular death. Rheumatoid arthritis (RA) patients (pts) were shown to have higher NT-proBNP concentrations than in general population, but it remains unclear, whether NT-proBNP levels are related to RA duration, activity or treatment.Objectives:To investigate the effect of interleukin 6 receptor inhibitor - tocilizumab (TCZ) and JAK inhibitor - tofacitinib (TOFA) on NT-proBNP levels in RA pts during a 12-month (m) follow-up period.Methods:The study enrolled 60pts (50women/10men) with the lack of efficacy/resistance and/or intolerance of basic anti-inflammatory drugs (DMARDs); median age was 55[42;61] years, median disease duration 55[29;120]m, with moderate to high activity (DAS28-5,1[4,6;6,1], serum positivity for rheumatoid factor (RF)(85%)/ anti-cyclic citrullinated peptide antibodies (ACCP)(80%). The study did not include RA pts with CHF and clinically overt cardiovascular disease (CVD). Twenty nine RA pts received TCZ(8mg/kg) every 4 weeks: 61% received TCZ in combination with methotrexate (MTX), 35% - with low-dose glucocorticoids (GCs). Thirty one RA pts were prescribed oral TOFA at 5 mg BID with dose escalation to 10 mg BID in 8 (26%)pts. TOFA was used in combination with MTX in 90% pts, with GCs – in 29% pts. Pts treated with TCZ and TOFA were comparable in terms of age, sex, body mass index. RA activity rates (DAS28, SDAI, ESR, CRP) were higher in pts on TCZ -therapy compared with pts treated with TOFA. Echocardiography data and NT-proBNP levels using electrochemiluminescence method Elecsys proBNP II (Roche Diagnostics, Switzerland) were obtained at baseline and after 12m.Results:Significant positive changes in major disease activity, clinical and laboratory parameters were found in RA pts after 12 m of TCZ infusion and TOFA intake: remission (DAS28<2,6) was achieved in 54% and 39% pts, low activity levels (DAS28<3,2) – in 46% and 51% pts, respectively.The NT-proBNP levels were significantly higher in RA pts than in the control group (median 69,1 (37,9;105,8) pg/mL vs 55,3 (36,6;67,3) pg/mL,p<0.05).Six pts (10%) (three in each pts group) had NT-proBNP levels over 125pg/ml, but were asymptomatic and had unremarkable echocardiography.There was a good correlation between NT-proBNP level at baseline with age (r=0,55,p<0,001), SDAI (r=0,5, h=0,01), ACCP (r=0,23,p=0,01).Decrease of median NT-proBNP levels was documented after 12m of TCZ therapy (81,5[43,0;102,0]vs41,6[25,4;64,2]pg/ml (p<0,01) and after 12m TOFA therapy (66,1[30,5;105,0]vs16,8 [5,0;81,0]pg/ml,p=0,001).After 12m of TCZ correlations of ΔNT-proBNP were established with ΔESR (R=0,43;p<0,05], ΔСRP (R=0,46;p<0,05], ΔEe left ventricle (LV) (r=0,88,p=0,03).In the group of pts treated with TOFA ΔNT-proBNP level significantly correlated with the percentage change in DAS 28 (r=0,41,p=0,038), there was no direct correlation with changes in the parameters of the LV diastolic function.Conclusion:TCZ and TOFA treatment for 12 m reduced NT-proBNP levels in RA pts without clinically manifest CVD and CHF. Falling NT-proBNP concentrations are associated with positive dynamics of RA activity (DAS 28) and inflammatory markers (CRP, ESR), therefore allowing to suggest that increased NT-proBNP levels should be considered as a component of disease activity. Correlation between ΔNT-proBNP and ΔEeLF may be indicative as possible impact of these biomarkers on the LV diastolic function’s development in RA pts.Disclosure of Interests:None declared

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