scholarly journals A genetic model of ivabradine recapitulates results from randomized clinical trials

2020 ◽  
Author(s):  
Marc-André Legault ◽  
Johanna Sandoval ◽  
Sylvie Provost ◽  
Amina Barhdadi ◽  
Louis-Philippe Lemieux Perreault ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Heart Rate ◽  
Drug Target ◽  
Drug Targets ◽  
Risk Model ◽  
Cardiovascular Death ◽  
Increased Risk ◽  
The Uk

ABSTRACTBackgroundNaturally occurring human genetic variants provide a valuable tool to identify drug targets and guide drug prioritization and clinical trial design. Ivabradine is a heart rate lowering drug with protective effects on heart failure despite increasing the risk of atrial fibrillation. In patients with coronary artery disease without heart failure, the drug does not protect against major cardiovascular adverse events prompting questions about the ability of genetics to have predicted those effects. This study evaluates the effect of a mutation in HCN4, ivabradine’s drug target, on safety and efficacy endpoints.MethodsWe used genetic association testing and Mendelian randomization to predict the effect of ivabradine and heart rate lowering on cardiovascular outcomes.ResultsUsing data from the UK Biobank and large GWAS consortia, we evaluated the effect of a heart rate-reducing genetic variant at the HCN4 locus encoding ivabradine’s drug target. These genetic association analyses showed increases in risk for atrial fibrillation (OR 1.09, 95% CI: 1.06-1.13, P=9.3 ×10−9) in the UK Biobank. In a cause-specific competing risk model to account for the increased risk of atrial fibrillation, the HCN4 variant reduced incident heart failure in participants that did not develop atrial fibrillation (HR 0.90, 95% CI: 0.83-0.98, P=0.013). In contrast, the same heart rate reducing HCN4 variant did not prevent a composite endpoint of myocardial infarction or cardiovascular death (OR 0.99, 95% CI: 0.93-1.04, P=0.61).ConclusionGenetic modelling of ivabradine recapitulates its benefits in heart failure, promotion of atrial fibrillation, and neutral effect on myocardial infarction.CONDENSED ABSTRACTThe effects of drugs can sometimes be predicted from the effects of mutations in genes encoding drug targets. We tested the effect of a heart rate reducing allele at the HCN4 locus encoding ivabradine’s drug target and found results coherent with the SHIFT and SIGNIFY clinical trials of ivabradine. The genetic variant increased the risk of atrial fibrillation and cardioembolic stroke and protected against heart failure in a competing risk model accounting for the increased risk of atrial fibrillation. The variant had a neutral effect on a composite of myocardial infarction and cardiovascular death.

Myocardial reperfusion reverses the J-curve association of cardiovascular risk and diastolic blood pressure in patients with left ventricular dysfunction and heart failure after myocardial infarction: insights from the EPHESUS trial

2020 ◽  
Vol 41 (17) ◽  
pp. 1673-1683 ◽  
Author(s):  
Michael Böhm ◽  
João Pedro Ferreira ◽  
Felix Mahfoud ◽  
Kevin Duarte ◽  
Bertram Pitt ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Cox Regression ◽  
Cardiovascular Death ◽  
Left Ventricular ◽  
Coronary Perfusion ◽  
Increased Risk ◽  
The Impact

Abstract Aims The described association of low diastolic blood pressure (DBP) with increased cardiovascular outcomes could be due to reduced coronary perfusion or is simply due to reverse causation. If DBP is physiologically relevant, coronary reperfusion after myocardial infarction (MI) might influence DBP–risk association. Methods and results The relation of achieved DBP with cardiovascular death or cardiovascular hospitalization, cardiovascular death, and all-cause death was explored in 5929 patients after acute myocardial infarction (AMI) with impaired left ventricular function, signs and symptoms of heart failure, or diabetes in the EPHESUS trial according to their reperfusion status. Cox regression models were used to assess the impact of reperfusion status on the association of DBP and systolic blood pressure (SBP) with outcomes in an adjusted fashion. In patients without reperfusion, lower DBP <70 mmHg was associated with increased risk for all-cause death [adjusted hazard ratios (HRs) 1.80, 95% confidence interval (CI) 1.41–2.30; P < 0.001], cardiovascular death (HR 1.70, 95% CI 1.3–3.22; P < 0.001), cardiovascular death or cardiovascular hospitalization (HR 1.54, 95% CI 1.26–1.87; P < 0.001). In patients with reperfusion, the risk increase at low DBP was not observed. At low SBP, risk increased independently of reperfusion. A sensitivity analysis in the subgroup of patients with optimal SBP of 120–130 mmHg showed again risk reduction of reperfusion at low DBP. Adding the treatment allocation to eplerenone or placebo into the models had no effects on the results. Conclusion Patients after AMIs with a low DBP had an increased risk, which was sensitive to reperfusion therapy. Low blood pressure after MI identifies in patients with particular higher risk. These data support the hypothesis that low DBP in patients with stenotic coronary lesions is associated with risk, potentially involving coronary perfusion pressure and the recommendations provided by guidelines suggesting lower DBP boundaries for these high-risk patients.

Abstract 15224: Importance of Beta Blocker Subtype for the Risk of Perioperative Adverse Events in Patients Without Heart Failure and Myocardial Infarction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Mads E Jørgensen ◽  
Gunnar H Gislason ◽  
Christian Torp-Pedersen ◽  
Mark Hlatky ◽  
C harlotte Andersson
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Beta Blocker ◽  
Beta Blockers ◽  
Cardiovascular Death ◽  
Adverse Outcomes ◽  
Major Adverse Cardiovascular Events ◽  
Blocker Therapy ◽  
Beta Blocker Therapy ◽  
Increased Risk

Objective: Beta blocker therapy in patients undergoing surgery is being revisited. Previous studies have demonstrated increased risks of perioperative adverse outcomes associated with beta blocker therapy, but whether some beta blocker subtypes may be superior to others remains unknown. Methods: Using nationwide Danish registries we included all non-cardiac surgeries in patients without heart failure or myocardial infarction in 2005-2011. Patients were grouped according to beta blocker use prior to surgery. Risks of 30-day MACE (major adverse cardiovascular events; non-fatal myocardial infarction, non-fatal stroke or cardiovascular death) were estimated using logistic regression models adjusted for gender, age, body mass index, pharmacotherapy, comorbidities, type of surgery and surgery risk. Results: We included 607,338 patients in the study. Patients on beta blockers (n=50,480) were older with similar gender distribution (mean age 66 years [sd=12.9], 45%male) compared with patients not on beta blockers (n=556,858) (mean age 52 years [sd=17.6], 44%male). Patients on beta blockers had more comorbidities and received more pharmacotherapy (all p<0.001). Unadjusted absolute risks of MACE were increased with all beta blocker subtypes (range 1.7% for propranolol to 4.2% for sotalol) compared with untreated patients (0.8%). Odds ratios for the risk of 30-day MACE are shown in the Figure Conclusion: Patients without chronic heart failure and prior myocardial infarction were at increased risk of 30-day perioperative MACE when treated with beta blockers, with the exception of bisoprolol. Patients treated with carvedilol seemed to be at especially high risk.

scholarly journals The association of digoxin with mortality in ischemic heart failure: a secondary analysis of the STICH trial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Pandya ◽  
D.L Brown
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Medical Therapy ◽  
Proportional Hazards ◽  
Cardiovascular Death ◽  
Cox Proportional Hazards ◽  
Ischemic Heart ◽  
Ischemic Heart Failure ◽  
Increased Risk ◽  
All Cause Mortality

Abstract Background Digoxin, one of the first treatments for symptoms of congestive heart failure (CHF), is currently used in the management of persistent CHF symptoms as well as for ventricular rate control in atrial fibrillation. Current guidelines suggest digoxin as an adjunct to optimal medical therapy for symptomatic improvement in CHF. However, the data regarding the effect of digoxin use on mortality continue to be conflicting. Purpose The aim of this retrospective study was to evaluate the association of digoxin therapy with mortality in patients with ischemic heart failure defined by severe left ventricular (LV) dysfunction and coronary artery disease (CAD) in the Surgical Treatment for Ischemic Heart Failure (STICH) trial. Methods STICH randomized 1012 patients with CAD and LV ejection fraction&lt;35% to coronary artery bypass graft (CABG) surgery and medical therapy vs. medical therapy alone. Factors predictive of digoxin use were identified with a binomial logistic regression model. Multivariable Cox proportional hazards modelling was performed with digoxin use modelled as a segmented time-dependent covariate. The model was adjusted for baseline clinical characteristics (including age, race, hypertension, hyperlipidemia, diabetes mellitus, peripheral vascular disease, NYHA heart failure class, previous myocardial infarction, atrial fibrillation, creatinine level, smoking status, and STICH treatment group) and stratified based on sex. All covariates were verified to meet the proportional hazards assumption. The primary outcome was all-cause mortality. Secondary outcomes included death and hospitalization due to cardiovascular causes. Relative risks were expressed as adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Results Of the 1012 patients, 351 (35% [36% of male patients and 27% of female patients]) reported digoxin use for some duration during the study period. Significant predictors of digoxin use included minority status, NYHA class, previous myocardial infarction, and baseline diagnosis of hypertension, diabetes, or atrial fibrillation. At a mean follow-up of 9.8 years, 566 patients (55.7%) experienced all-cause mortality and 387 patients (38.1%) died due to cardiovascular causes. The adjusted Cox proportional hazards model demonstrated that digoxin use was independently associated with an increased risk of all-cause mortality (aHR 1.22, 95% CI: 1.00–1.49, P=0.049). Digoxin use was also associated with increased risk of cardiovascular death (aHR 1.29, 95% CI: 1.02–1.64, P=0.032). There was no impact of digoxin on hospitalization for cardiovascular causes. Conclusion Use of digoxin in patients with ischemic heart failure was associated with an increased risk of both all-cause and cardiovascular death. Funding Acknowledgement Type of funding source: None

scholarly journals Association between Atrial Fibrillation, Myocardial Infarction, Heart Failure and Mortality in Patients with Nontuberculous Mycobacterial Infection: a nationwide population-based study

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chan Soon Park ◽  
Eue-Keun Choi ◽  
Bongseong Kim ◽  
Kyung-Do Han ◽  
So-Ryoung Lee ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Mycobacterial Infection ◽  
Population Based ◽  
Newly Diagnosed ◽  
Increased Risk ◽  
Significant Difference ◽  
Risk Patients ◽  
The Impact

Abstract NTM infection demonstrates an increasing incidence and prevalence. We studied the impact of NTM in cardiovascular events. Using the Korean nationwide database, we included newly diagnosed 1,730 NTM patients between 2005 and 2008 and followed up for new-onset atrial fibrillation (AF), myocardial infarction (MI), heart failure (HF), ischemic stroke (IS), and death. Covariates-matched non-NTM subjects (1:5, n = 8,650) were selected and analyzed. Also, NTM infection was classified into indolent or progressive NTM for risk stratification. During 4.16 ± 1.15 years of the follow-up period, AF, MI, HF, IS, and death were newly diagnosed in 87, 125, 121, 162, and 468 patients. In multivariate analysis, NTM group showed an increased risk of AF (hazard ratio [HR] 2.307, 95% confidence interval [CI] 1.560–3.412) and all-cause death (HR 1.751, 95% CI 1.412–2.172) compared to non-NTM subjects, whereas no significant difference in MI (HR 0.868, 95% CI 0.461–1.634), HF (HR 1.259, 95% CI 0.896–2.016), and IS (HR 1.429, 95% CI 0.981–2.080). After stratification, 1,730 NTM patients were stratified into 1,375 (79.5%) indolent NTM group and 355 (20.5%) progressive NTM group. Progressive NTM showed an increased risk of AF and mortality than indolent NTM group. Screening for AF and IS prevention would be appropriate in these high-risk patients.

scholarly journals Primary prevention of atrial fibrillation in patients with metabolic syndrome: correction of modifiable risk factors

2021 ◽  
Vol 6 (2) ◽  
pp. 103-115
Author(s):  
A. I. Olesin ◽  
I. V. Konstantinova
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Metabolic Syndrome ◽  
Primary Prevention ◽  
High Risk ◽  
Modifiable Risk Factors ◽  
Financial Costs ◽  
Increased Risk

Currently, around 34 million people worldwide suffer from atrial fibrillation (AF), with the number projected to double by 2060. Despite the treatment of AF has been significantly improved during the recent years, AF is still associated with an increased risk of severe complications such as systemic thromboembolism, progression of heart failure, stroke, and myocardial infarction. Due to a high risk of disability and mortality, AF represent a major socioeconomic problem for the healthcare in most countries, also because of related financial costs. Obesity, most often represented by metabolic syndrome, is widely recognized as an epidemic of the XXI century. Here we review the features of AF development in patients with metabolic syndrome, suggesting novel avenues for the primary prevention of AF. 

scholarly journals The impact of growth differentiation factor 15 on the risk of cardiovascular diseases: two-sample Mendelian randomization study

2020 ◽  
Author(s):  
Zhuo Wang ◽  
Fangkun Yang ◽  
Menghuai Ma ◽  
Qinyi Bao ◽  
Jinlian Shen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Coronary Artery Disease ◽  
Mendelian Randomization ◽  
Large Artery ◽  
Nonischemic Cardiomyopathy ◽  
Growth Differentiation Factor 15 ◽  
Increased Risk ◽  
Artery Disease

Abstract Background: Growth differentiation factor 15 (GDF-15), a stress responsive cytokine, belongs to transforming growth factor β (TGF-β) cytokine superfamily. Some evidence support that it’s involved in inflammation, coagulation, oxidative stress, endothelial dysfunction, and hemostasis. However, it’s still controversial whether GDF-15 directly contributes to the morbidity and mortality of patients suffered with cardiovascular disease (CVD). Besides prospective cohort study and randomized controlled trial, Mendelian randomization (MR) is a genetic epidemiological method that exploits genetic variants as unbiased proxies for modifiable to determine the causal relationships between exposures and health outcomes. Herein, we introduced a two-sample MR approach to evaluate the causal relationships of circulating GDF-15 levels with major CVDs incidence.Methods: Genetic instruments and summary statistics for two-sample MR analysis were obtained from 5 independent large genome-wide association studies (GWAS) to investigate the causal correlation between circulating GDF-15 levels and 9 CVDs, respectively. Conventional inverse variance weighted (IVW) method was adopted to evaluate the causality of GDF-15 with different outcomes; weighted median and MR egger were used for sensitivity analyses.Results: Among 9 SNPs identified from 5 GWASs in 2.6 million individuals, 5 SNPs (rs1227731, rs3195944, rs17725099, rs888663, rs749451) coming from chromosome 19 and containing the PGPEP1 and GDF-15 genes were employed. Based on the instruments, circulating GDF-15 levels significantly linked to the increased risk of cardioembolic stroke, atrial fibrillation, coronary artery disease and myocardial infarction. However, no significant causal association was observed for circulating GDF-15 levels with the incidence of any ischemic stroke, large-artery atherosclerotic stroke, small vessel stroke, heart failure and nonischemic cardiomyopathy.Conclusions: The MR study provides with genetic evidence for the causal relationship of circulating GDF-15 levels with the increased risk of cardioembolic stroke, atrial fibrillation, coronary artery disease and myocardial infarction, but not any ischemic stroke, large-artery atherosclerotic stroke, small vessel stroke, heart failure and nonischemic cardiomyopathy. It indicates that GDF-15 might be a promising biomarker or potential therapeutic target for some CVDs.

Factors predicting adverse cardiovascular outcomes in patients with atrial fibrillation and heart failure with preserved ejection fraction

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
S Saksena ◽  
APRIL Slee ◽  
D Lakkireddy ◽  
DIPEN Shah ◽  
LUIGI Di Biase ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Heart Rate ◽  
Ejection Fraction ◽  
Cox Model ◽  
Cardiovascular Death ◽  
Adverse Outcomes ◽  
P Value ◽  
Preserved Ejection Fraction ◽  
Pump Failure

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Electrophysiology Research Foundation Introduction Atrial fibrillation (AF) is known to impact cardiovascular(CV) mortality in heart failure (HF) patients (pts) with preserved ejection fraction (pEF) but its exact causes are unknown. Methods  We analyzed demographic, clinical, ECG and AF presentation as predictors of CV mortality, sudden death( SCD) and pump failure death(PFD) in HFpEF pts in the TOPCAT AMERICAS trial. We analyzed two AF presentations 1. Pts in sinus rhythm (SR, n = 1319) compared to AF  on ECG (n = 446) at entry or 2. Pts with no AF event by history or ECG ( n = 1007 ) to those with any AF event (n = 760 ). Results (Table): 5 year (yr) CV mortality was higher in pts with AF on ECG (30%) than SR (18%, p = 0.014) but 5 yr SCD was (10% in AF on ECG & 7% in any AF) & comparable to SR (7% & 9% respectively, p = ns). 5 yr PFD was higher in AF on ECG  (13%) than SR (5%, p = 0.007)  Conclusions : 1. CV death risk in HFpEF pts increased with AF on ECG.. 2. SCD was not more frequent with both AF presentations 3. PFD in HFpEF increased with age, ECG recorded AF & elevated heart rate. 4. The recording of AF on ECG was more strongly associated with CV death & PFD, possibly due to greater AF burden . Predictors of adverse outcomes in HFpEF AF on ECG* Any AF* Endpoint Covariate HR (95% CI) p-value HR (95% CI) p-value Time to cardiovascular death Atrial Fibrillation* 1.44 (1.08, 1.92) 0.014 1.15 (0.87, 1.51) 0.338 Age (years) 1.03 (1.02, 1.05) &lt;.001 1.03 (1.02, 1.05) &lt;.001 Black/AA (vs. White) 0.97 (0.65, 1.46) 0.002 0.96 (0.64, 1.44) 0.004 Other race (vs. White) 2.41 (1.46, 3.99) 2.32 (1.41, 3.83) Smoking 2.62 (1.63, 4.20) &lt;.001 2.60 (1.62, 4.17) &lt;.001 Diabetes 1.47 (1.12, 1.94) 0.006 1.45 (1.10, 1.91) 0.009 Systolic BP (mmHg) 0.99 (0.98, 1.00) 0.022 0.99 (0.98, 1.00) 0.014 Heart rate (bpm) 1.02 (1.00, 1.03) 0.012 1.02 (1.01, 1.03) 0.006 Time to Any sudden cardiac death Atrial Fibrillation* 1.17 (0.69, 1.96) 0.563 0.85 (0.53, 1.35) 0.484 Female (vs. Male) 0.46 (0.28, 0.75) 0.002 0.46 (0.28, 0.74) 0.002 Black/AA (vs. White) 1.57 (0.87, 2.82) 0.194 1.49 (0.83, 2.69) &lt;.001 Other race (vs. White) 1.76 (0.70, 4.41) 1.70 (0.68, 4.25) Diabetes 1.70 (1.07, 2.70) 0.024 1.65 (1.04, 2.62) 0.033 Time to pump failure death Atrial Fibrillation* 2.04 (1.22, 3.42) 0.007 1.62 (0.96, 2.75) 0.074 Age (years) 1.06 (1.03, 1.10) &lt;.001 1.06 (1.03, 1.10) &lt;.001 Heart rate (bpm) 1.03 (1.00, 1.05) 0.034 1.03 (1.01, 1.05) 0.015 Cox model of covariates associated with outcomes adjusted for baseline imbalances

scholarly journals Psoriasis and Psoriatic Arthritis Cardiovascular Disease Endotypes Identified by Red Blood Cell Distribution Width and Mean Platelet Volume

2020 ◽  
Vol 9 (1) ◽  
pp. 186 ◽  
Author(s):  
Rosalynn RZ Conic ◽  
Giovanni Damiani ◽  
Kory P. Schrom ◽  
Amy E. Ramser ◽  
Chunlei Zheng ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Psoriatic Arthritis ◽  
Chronic Heart Failure ◽  
Mean Platelet Volume ◽  
Cell Distribution ◽  
Platelet Volume ◽  
Distribution Width ◽  
Increased Risk

In a subset of psoriasis (PsO) and psoriatic arthritis (PsA) patients, the skin and/or joint lesions appear to generate biologically significant systemic inflammation. Red cell distribution width (RDW) and mean platelet volume (MPV) are readily available clinical tests that reflect responses of the bone marrow and/or plasma thrombogenicity (e.g., inflammation), and can be markers for major adverse cardiac events (MACE). We aimed to evaluate if RDW and MPV may be employed as inexpensive, routinely obtained biomarkers in predicting myocardial infarction (MI), atrial fibrillation (AF), and chronic heart failure (CHF) in psoriatic and psoriatic arthritis patients. The study was divided into two parts: (a) case control study employing big data (Explorys) to assess MPV and RDW in psoriasis, psoriatic arthritis and control cohorts; (b) a clinical observational study to validate the predictive value of RDW and to evaluate RDW response to anti-psoriatic therapies. We used Explorys, an aggregate electronic database, to identify psoriatic patients with available MPV and RDW data and compared them to gender and age matched controls. The incidence of myocardial infarction (MI), atrial fibrillation (AF), and chronic heart failure (CHF) was highest among patients with both elevated RDW and MPV, followed by patients with high RDW and normal MPV. RDW elevation among PsA patients was associated with an increased risk of MI, AF, and CHF. In a local clinical cohort, high RDWs were concentrated in a subset of patients who also had elevated circulating resistin levels. Among a small subset of participants who were treated with various systemic and biologic therapies, and observed over a year, and in whom RDW was elevated at baseline, a sustained response to therapy was associated with a decrease in RDW. RDW and MPV, tests commonly contained within routine complete blood count (CBC), may be a cost-effective manner to identify PsO and PsA patients at increased risk of MACE.

scholarly journals The impact of growth differentiation factor 15 on the risk of cardiovascular diseases: two-sample Mendelian randomization study

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhuo Wang ◽  
Fangkun Yang ◽  
Menghuai Ma ◽  
Qinyi Bao ◽  
Jinlian Shen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Coronary Artery Disease ◽  
Mendelian Randomization ◽  
Large Artery ◽  
Nonischemic Cardiomyopathy ◽  
Growth Differentiation Factor 15 ◽  
Increased Risk ◽  
Artery Disease

Abstract Background Growth differentiation factor 15 (GDF-15), a stress responsive cytokine, belongs to transforming growth factor β cytokine superfamily. Some evidence support that it’s involved in inflammation, coagulation, oxidative stress, endothelial dysfunction, and hemostasis. However, it’s still controversial whether GDF-15 directly contributes to the morbidity and mortality of patients suffered with cardiovascular disease (CVD). Besides prospective cohort study and randomized controlled trial, Mendelian randomization (MR) is a genetic epidemiological method that exploits genetic variants as unbiased proxies for modifiable to determine the causal relationships between exposures and health outcomes. Herein, we introduced a two-sample MR approach to evaluate the causal relationships of circulating GDF-15 levels with major CVDs incidence. Methods Genetic instruments and summary statistics for two-sample MR analysis were obtained from 5 independent large genome-wide association studies (GWAS) to investigate the causal correlation between circulating GDF-15 levels and 9 CVDs, respectively. Conventional inverse variance weighted method was adopted to evaluate the causality of GDF-15 with different outcomes; weighted median and MR egger were used for sensitivity analyses. Results Among 9 SNPs identified from 5 GWASs in 2.6 million individuals, 5 SNPs (rs1227731, rs3195944, rs17725099, rs888663, rs749451) coming from chromosome 19 and containing the PGPEP1 and GDF-15 genes were employed. Based on the instruments, circulating GDF-15 levels significantly linked to the increased risk of cardioembolic stroke, atrial fibrillation, coronary artery disease and myocardial infarction. However, no significant causal association was observed for circulating GDF-15 levels with the incidence of any ischemic stroke, large-artery atherosclerotic stroke, small vessel stroke, heart failure and nonischemic cardiomyopathy. Conclusions The MR study provides with genetic evidence for the causal relationship of circulating GDF-15 levels with the increased risk of cardioembolic stroke, atrial fibrillation, coronary artery disease and myocardial infarction, but not any ischemic stroke, large-artery atherosclerotic stroke, small vessel stroke, heart failure and nonischemic cardiomyopathy. It indicates that GDF-15 might be a promising biomarker or potential therapeutic target for some CVDs.

Long-term impact of the burden of new-onset atrial fibrillation in patients with acute myocardial infarction: data from the NOAFCAMI-SH registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S.L Xu ◽  
J Luo ◽  
H.Q Li ◽  
Z.Q Li ◽  
B.X Liu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Acute Myocardial Infarction ◽  
Ischemic Stroke ◽  
Cardiovascular Death ◽  
Funding Source ◽  
Onset Atrial Fibrillation ◽  
New Onset

Abstract Background The prognostic implication of the burden of paroxysmal new-onset atrial fibrillation (NOAF) in patients with acute myocardial infarction (AMI) remains unclear. We aimed to determine the impact of NOAF burden on long-term cardiovascular outcomes in the setting of AMI. Methods This retrospective study was conducted to investigate the association of NOAF burden with the major adverse cardiac events (MACE, a composite of cardiovascular death, recurrent MI, worsening of heart failure, or ischemic stroke), using data from the New Onset Atrial Fibrillation Complicating Acute Myocardial Infarction in ShangHai registry. AF burden was defined as the percentage of time (%) spent in AF. Patients with paroxysmal NOAF were divided into three groups according to AF burden tertiles: low burden: 22.4%. A restricted cubic spline analysis was performed to illusrate the relationship between the burden of NOAF and MACE. Results Of 2399 participants, 278 developed NOAF during a median monitoring period of 194.9 hours. The mean age was 65.8±12.4 years, and the median burden of NOAF was 8.4% (IQR: 1.9%-38.1%). During up to 5-years follow-up, the incidence of MACE was 8.6, 17.4, 35.4, and 79.2 per 100 person-years in the sinus rhythm, low-, intermediate-, and high-burden groups, respectively. After adjustment, patients with high NOAF burden had the highest risk of MACE (hazard ratio [HR]: 3.10; 95% confidence interval [CI]: 2.36–4.07), cardiovascular death (HR: 2.26; 95% CI: 1.58–2.23), worsening of heart failure (HR: 4.90; 95% CI: 3.48–4.91), and ischemic stroke (HR: 4.42; 95% CI: 2.03–9.63). Our splines analyses uncovered a nonlinear dose-response pattern, as the HRs of MACEs increased with the progression of NOAF burden and appeared stable after approximately 15% of NOAF burden. Conclusions A greater burden of NOAF during AMI was strongly associated with a higher risk of adverse cardiovascular events. Cumulative incidence of outcomes Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): 1. National Natural Science Foundation of China, 2. Natural Science Foundation of Shanghai

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