Cumulative Incidence Of Cardiovascular Death Research Articles

Association of the panimmune-inflammatory value (PIV) with all-cause and cardiovascular mortality in maintenance hemodialysis patients: a propensity score matching retrospective study.

The panimmune-inflammatory value (PIV) is a novel inflammatory indicator. However, its role in maintenance hemodialysis (MHD) remains unclear. Our goal was to explore the predictive value of PIV for cardiovascular and all-cause mortality in MHD patients. In this retrospective cohort study, 507 patients receiving MHD between November 2017 and December 2022 were enrolled. The PIV value was calculated as follows: neutrophil count × monocyte count × platelet count/lymphocyte count. Patients were divided into two groups on the basis of the median PIV. Propensity score matching (PSM) was used to adjust for imbalances in baseline information between groups. Kaplan‒Meier curves, Cox regression, the Fine‒Gray competing risk model, and restricted cubic spline (RCS) curves were used to analyze the relationship between PIV and mortality. By the end of follow-up, 126 deaths had occurred, 91 of which were due to cardiovascular disease. The Kaplan‒Meier curves demonstrated that MHD patients with higher PIV levels had a poorer prognosis for all-cause death (p = 0.019). PIV levels were linked to all-cause death in multivariate Cox proportional risk regression (HR = 1.76; 95% CI 1.14, 2.72; p = 0.011). The Fine‒Gray model revealed a greater cumulative incidence of cardiovascular death in the higher PIV group (p = 0.035). PIV levels were linked to cardiovascular mortality in the Fine‒Gray competing risk model (HR = 2.06; 95% CI 1.25, 3.42; p = 0.005). The RCS revealed a nonlinear relationship between PIV and mortality risk (p < 0.05). Using 63years of age as the threshold, we observed a multiplicative interaction effect between age and PIV for all-cause mortality (p = 0.006). In MHD patients, PIV is an independent hazard factor for cardiovascular-related mortality and all-cause mortality.

Analysis of competing risks of cardiovascular death in patients with hepatocellular carcinoma: A population-based study.

Clinical data has shown that cardiovascular diseases (CVDs) have emerged as a prominent cause of mortality in individuals with hepatocellular carcinoma (HCC). This research aimed to reveal the comorbid effects of CVDs in patients with HCC. The cardiovascular mortality of patients diagnosed with HCC between 2000 and 2014 was compared to that of the general US population. Standardized mortality ratios were calculated to quantify the relative risk of cardiovascular mortality in HCC patients. The cumulative incidence of cardiovascular death (CVD) was estimated using Fine-Gray testing, and independent risk factors for CVD were determined using competing risk models. The results were analyzed using the Kaplan-Meier analysis. The overall SMR for CVD in HCC patients was 11.15 (95% CI: 10.99-11.32). The risk of CVD was significantly higher in patients aged < 55 years (SMR: 56.19 [95% CI: 54.97-57.44]) compared to those aged ≥ 75 years (SMR: 1.86 [95% CI: 1.75-1.97]). This study suggests that patients with HCC are at significant risk of developing CVD. Competing risk analyses indicated that age, grade, tumor size, surveillance, epidemiology, and end results stage, and surgical status were independent risk factors for CVD in patients with HCC. Therefore, patients with HCC require enhanced preventive screening and management of CVDs during and after treatment to improve patient survival.

Involvement of growth differentiation factor 15 in paradoxical relationship between body mass index and mortality in patients with suspected or known coronary artery disease; The ANOX Study

Abstract Background Obesity is a well-established risk factor for type 2 diabetes mellitus, hypertension and dyslipidemia, leading to coronary artery disease (CAD). Nevertheless, body mass index (BMI) is inversely associated with cardiovascular (CV) mortality in patients with cardiac disorders, termed “obesity paradox”. However, the underlying mechanism remains unclear. Purpose To clarify important factors involved in the pathogenesis of obesity paradox. Methods Using data from a multicenter, prospective cohort of 2,418 patients with suspected or known CAD enrolled in the ANOX study, we assessed the relationship between BMI at baseline and the incidence of CV death over 3 years, and investigated the involvement of several endocrine factors which were previously reported to have some roles in obesity and heart diseases, such as adiponectin, N-terminal pro-brain natriuretic peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15), in the relationship between BMI and CV death. Results In Kaplan-Meier analyses, the lower quartiles of BMI and the higher quartiles of adiponectin levels were paradoxically associated with the higher cumulative incidence of CV death. To clarify the important factors involved in the paradoxical association between BMI or adiponectin and mortality, we first investigated independent determinants for BMI and adiponectin levels respectively, using multiple stepwise regression analyses among many clinical factors, and then narrow down the prognostic factors commonly associated with BMI and adiponectin, which were age, hemoglobin and NT-proBNP. Interestingly, circulating levels of GDF15 were significantly correlated with NT-proBNP levels, and the presence of anemia raised the gradient of the correlation line in a scatter plot (without anemia, r=0.139, p&amp;lt;0.0001; with anemia, r=0.228, p&amp;lt;0.0001). Moreover, the highest GDF15 quartile showed significantly lower BMI and higher adiponectin levels compared to the lower quartiles (p&amp;lt;0.001 and p&amp;lt;0.001, respectively, by Student t-test). In Cox proportional hazard models, hazard ratios (HRs) of BMI (per 1-unit increase) were 0.90 (95% confidence interval [CI], 0.85–0.96) for CV death. Additional adjustment for hemoglobin, NT-proBNP, adiponectin or GDF15 diminished the statistical significance (HR, 0.92 [95% CI, 0.87–0.99], 0.95 [0.89–1.01], 0.92 [0.87–0.99], or 0.93 [0.87–0.99], respectively). Conclusions The lower BMI and the higher adiponectin levels were paradoxically associated with the higher incidence of CV death in patients with CAD. This paradox may be mediated by cardiac endocrine factors induced by cardiac stresses, including GDF-15 in addition to natriuretic peptides. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): The ANOX study is supported by a Grant-in-Aid for Clinical Research from the National Hospital Organization.

Utilization and Efficacy of Cardiac Resynchronization Therapy in Patients With Chronic Heart Failure - A Report From the CHART-2 Study.

Background: Although cardiac resynchronization therapy (CRT) is effective for patients with chronic heart failure (CHF) with reduced left ventricular ejection fraction and wide QRS (≥120 ms), data on the use of or long-term outcomes after CRT implantation in Japan are limited.Methods and Results: We examined proper CRT utilization and outcomes in 3,447 consecutive symptomatic CHF patients registered in the CHART-2 Study. We identified 167 potentially eligible patients and divided them into 4 groups according to the presence (+) or absence (−) of an indication for and implantation of CRT: Group A (reference group), (+)indication/(+)CRT; Group B, (+)indication/(−)CRT; Group C, (−)indication/(+)CRT; and Group D, (−)indication/(−)CRT. Based on the Japanese Circulation Society guidelines, 91 patients met the eligibility for CRT implantation, with 43 (47%) of them undergoing CRT implantation. After adjusting for confounders, age was significantly associated with no CRT use (odds ratio per 5-year increase 1.46; 95% confidence interval 1.11–2.05; P=0.012). Among the 4 groups, the cumulative incidence of cardiovascular death and CHF admission were highest in Group B and lowest in Group D (P=0.029).Conclusions: In this study, only half the eligible CHF patients properly received CRT. Aging was a significant risk factor for no CRT use. Patients without CRT despite having an indication could be at higher risk of mortality and CHF admission.

Gender difference in heart failure with preserved ejection fraction: clinical profiles, examinations, and prognosis

Heart failure with preserved ejection fraction (HFpEF) has currently become a major concern in the aging society owing to its substantial and growing prevalence. Recent investigations regarding sacubitril/valsartan have suggested that there is a gender difference in the efficacy of the medication in HFpEF cohort. However, information of gender difference in clinical profiles, examination, and prognosis have not been well investigated. The present study aimed to evaluate the differences in baseline characteristics and outcomes between women and men in a Japanese HFpEF cohort. We analyzed the data from our prospective, observational, and multicenter cohort study. Overall, 1036 consecutive patients hospitalized for acute decompensated heart failure were enrolled. We defined patients with an ejection fraction (EF) of ≥ 50% as HFpEF. Patients with severe valvular disease were excluded; the remaining 379 patients (women: n = 201, men: n = 178) were assessed. Women were older than men [median: 85 (79–89) years vs. 83 (75–87) years, p = 0.013]. Diabetes mellitus, hyperuricemia, and coronary artery disease were more prevalent in men than in women (34.8% vs. 23.9%, p = 0.019, 23.6% vs. 11.4%, p = 0.002, and 23.0% vs. 11.9%, p = 0.005, respectively). EF was not significantly different between women and men. The cumulative incidence of cardiovascular death or hospitalization for congestive heart failure (CHF) was significantly lower in women than in men (log-rank p = 0.040). Women with HFpEF were older and less often exhibited an ischemic etiology; further, they were associated with a lower risk for cardiovascular death or hospitalization for CHF compared with men in the Japanese population.

A Concomitant Cancer Diagnosis Is Associated With Poor Cardiovascular Outcomes Among Acute Myocardial Infarction Patients.

Background and AimsWith the increasing coexistence of cardiovascular disease and cancer in contemporary clinical practice, studies on the outcomes in acute myocardial infarction (AMI) patients with cancer has not been systematically investigated. This study sought to investigated the effect of coexisting cancer on the treatment and clinical outcomes among AMI patients.MethodsWe retrospectively integrated and analyzed cardiovascular data of 6,607 AMI patients between June 2016 and December 2019. Patients with cancer were compared with pair-matched cancer-naive patients. Cox proportional hazards models were constructed to compare the differences in outcomes.ResultsOf 6,607 patients, 2.3% (n = 150) had been diagnosed with cancer. Patients with cancer were older (70.3 ± 10.0 vs. 63.9 ± 11.5 years, P < 0.001) and had a higher burden of comorbidities. Moreover, patients with cancer tended to receive clopidogrel (52.0 vs. 40.0%, P = 0.004) rather than ticagrelor (45.6 vs. 58.2%, P = 0.003) than those without cancer. After pairwise matching, patients with cancer were less likely to undergo in-hospital percutaneous coronary intervention (61.3 vs. 70.0%, P = 0.055). And after 3-year follow-up, the cumulative incidence of cardiovascular death (14.0 vs. 8.3%; adjusted HR, 1.93; 95% CI, 1.11–3.39; P = 0.021) among patients with cancer was significantly higher than that among the matched controls, a similar pattern was observed for the composite outcome of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke (16.0 vs. 10.3%; adjusted HR, 1.98; 95% CI, 1.21–3.26; P = 0.007). Moreover, patients with a historical cancer diagnosis within 5 years had a higher risk of cardiovascular ischemic events.ConclusionsAMI patients with a concomitant diagnosis of cancer tended to be treated with conservative therapies and were at substantially higher risk for adverse cardiovascular outcomes.

Prognostic value of a normal Artificial Intelligence applicative response in subjects with stable chest pain. From the ARTICA co-operative registry

Abstract Background An innovative artificial intelligence (AI) Decision Support System (DSS) ESC guidelines based has already been used at point of care with efficacy for evaluating subjects with stable chest pain (SCP) and it has been proved to correctly identify absence of significant coronary artery disease (CAD) versus standard care approach (SD) without known prognostic implication yet. Purpose The aim is to determine the prognostic value of “no testing/Follow up” AI DSS response in a referral population evaluated for SCP. Methods From 2016 to 2019, an AI DSS ESC guidelines based applicative was used on 1.291 subjects with SCP to determine testing appropriateness compared with human specialist standard evaluation. 590 of them, 332 males, mean age 62±11 years deemed to be completely negative – by “no testing/follow up” response - were evaluated. The negative response was defined and confirmed by a normal Coronary Tomography Angiography scan executed in all these subjects. Mean follow-up was 3.46±1.76 years. Two groups based on pre-test likelihood of having CAD were analyzed – low and intermediate. No subjects with high pre-test likelihood were present. The primary endpoint was cumulative incidence of cardiovascular death, hospitalizations for acute coronary syndrome and coronary revascularizations. Results The primary endpoints classification is displayed in the Table. The unadjusted hazard ratio for primary endpoint was 3.84 (95% CI 0.32–8.68, p=0.009) in patients with intermediate compared to those with low pre-test likelihood of CAD. Moreover, the “no testing and Follow up” response showed an incremental prognostic value over conventional risk factors (χ2=7, P=0.022) and over a combination of conventional factors and ST-T changes (χ2=9, P=0.014). Conclusions In an outpatient population without known CAD evaluated for chest pain, after the administration of AI DSS, a “No tests/Follow up” confers an excellent prognosis regardless of the ESC SCORE Charts and rest ECG abnormalities. These preliminary data confirms the safety of ARTICA AI DSS use in subjects with stable chest pain. Funding Acknowledgement Type of funding source: None

Effect of beta blocker therapy following myocardial infarction in optimally treated patients in the reperfusion era – a Danish, nationwide, and registry-based cohort study

Abstract Background and purpose European and American cardiovascular treatment guidelines advocate for two and three years of beta-blocker (BB) treatment, respectively, following myocardial infarction (MI). Contemporary continued efficacy of longer-term use of BB in stable coronary artery disease has been debated in the era of reperfusion. We aim to investigate the cardio-protective effect associated with BB treatment in patients following MI. Methods Using nationwide databases, we included optimally treated patients with first-time MI undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI) during admission and treated with both acetyl-salicylic acid and statins post-discharge between 2003 and 2017. Patients with prior history of MI, BB use or any other possible indication or contraindication for BB treatment (heart failure, cardiac arrhythmias or procedures, asthma, chronic obstructive pulmonary disease) were excluded. Continued BB exposure was defined as two redeemed prescriptions within the first 180 days following discharge, one of them within 90 days. Follow-up began 180 days following discharge in patients alive and with no further cardiovascular events or procedures prior. Patients were followed for a maximum of three years. Primary outcomes were cardiovascular death and recurrent MI in patients stratified by BB treatment using adjusted Cox regression models. Results A total of 27,068 patients optimally treated for MI were included (57% acute PCI, 26% sub-acute PCI, 17% CAG without intervention). At study start 180 days following MI, 79% of the patients were on BB treatment (median age 61 years, 75% male) and 21% were not (median age 62 years, 69% male). Cumulative incidence of cardiovascular death and recurrent MI did not differ significantly comparing patients on BB treatment with patients not on BB treatment (Figure). In multivariable analyses, BB treatment was associated with a similar risk of cardiovascular death and recurrent MI compared to the patients not receiving BB treatment (hazard ratios with [95% confidence intervals] correspondingly; 0.89 [0.68–1.17] and 1.02 [0.89–1.18]) (Figure 1). When stratifying the cohort according to calendar year and type of procedure during admission, we found similar results as the main analysis. No interaction for sex was found. Conclusions In this nationwide cohort study of optimally treated patients following MI at 180 days in the reperfusion era, we found a very good prognosis with only 1.2% suffering cardiovascular death and 4.7% suffering a recurrent MI within three years. In total 79% of patients were receiving BB treatment, but we found no difference suggesting BB to be associated with an improved cardiovascular prognosis. These findings challenge current clinical practice and guideline recommendation, suggesting that the role of long-term BB use may be obsolete among optimally treated MI patients. Further investigations, preferably a randomized trial, are warranted. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Ib Mogens Kristiansens Almene Fond, Snedkermester Sophus Jacobsen og Hustru Astrid Jacobsens Fond

P2618Association of left ventricular ejection fraction with mortality and hospitalizations

Abstract Background Although 2-dimensional echocardiography (2DE) is widely used to measure left ventricular ejection fraction (LVEF), the prognostic value of 2DE-derived LVEF has not been clearly demonstrated in a broad range of patients, including those acutely hospitalized as well as ambulatory patients. In particular, the prognostic value of echocardiographic LVEF has not been demonstrated for cardiovascular and heart failure hospitalizations. Purpose To determine if greater degrees of LV dysfunction are associated with progressively increasing risks of death or cardiovascular hospitalizations among patients undergoing echocardiography in hospital or outpatient settings. Methods We examined quantitative LVEFs from patient-level echocardiographic reports at 3 large hospital laboratories, which were linked to the Canadian Institute for Health Information hospitalization database and to death registries in Ontario, Canada. LVEF was categorized as &lt;25%, 25–35%, 36–45%, or 46–55% (reference). Analyses were performed using cause-specific hazard competing risk models and stratified by: a) outpatient vs. inpatient echocardiogram, and b) if inpatient study, whether the reason for hospitalization was cardiac or noncardiac in nature. Results In the echocardiographic cohort of 27,323 patients (median age 68 [IQR: 58–77], 14,828 women [31.7%]), greater reductions in LVEF were associated with higher rates of all-cause mortality, with adjusted hazard ratios (95% CI) of 1.67 (1.57, 1.77) for LVEF &lt;25%, 1.30 (1.24, 1.36) for LVEF 25–35%, and 1.17 (1.11, 1.23) for LVEF 36–45%, compared to LVEF 46–55% (all p&lt;0.001). The cumulative incidence of cardiovascular death was higher as LVEF progressively worsened (Figure). The rate of heart failure hospitalizations was also increased with hazard ratios of 1.71 (1.59, 1.85) for LVEF &lt;25%, 1.39 (1.31, 1.48) for LVEF 25–35%, and 1.21 (1.13, 1.29) for LVEF 36–45%, compared to LVEF 46–55% (all p&lt;0.001). Cardiovascular hospitalizations were also increased with hazard ratios of 1.35 (1.27, 1.42), 1.21 (1.16, 1.27), and 1.13 (1.07, 1.18) for LVEFs &lt;25%, 25–35%, and 36–45%, respectively (all p&lt;0.001). The risk of mortality and hospitalizations increased comparably with greater reductions in LVEF during both inpatient cardiac or noncardiac admissions (p&lt;0.001). Cumulative incidence of CV death Conclusions Quantitative LVEF assessed by 2DE is potent prognostically and was able to stratify the risk of both death and hospitalization outcomes in a wide range of clinical settings. Patients with reduced LVEF measured on inpatient or outpatient echocardiograms, and even in the context of non-cardiac admission, should be considered an at-risk group in whom quality of care metrics could be evaluated in future studies. Acknowledgement/Funding Canadian Institutes of Health Research, Heart and Stroke Foundation, and the Ted Rogers Centre for Heart Research

Clinical utility of circulating interleukin-6 concentrations in the detection of functionally relevant coronary artery disease

BackgroundInflammation plays a major role in the pathogenesis of coronary artery disease (CAD). MethodsWe hypothesized, that quantifying inflammation by measuring circulating interleukin-6 concentrations help in the diagnosis and/or prediction of functionally relevant CAD. Among consecutive patients with symptoms suggestive of CAD, functionally relevant CAD was adjudicated in two domains: first, diagnosis according to myocardial perfusion single photon emission tomography (MPI-SPECT) and coronary angiography; second, cardiovascular death and all-cause death during 2-years follow-up. Adjudication was done blinded to the interleukin-6 concentrations. ResultsAmong 1553 patients, symptoms were adjudicated to be causally related to CAD in 43% (665/1553). Interleukin-6 concentrations were higher in patients with functionally relevant CAD as compared to those without (1.56 pg/mL versus 1.30 pg/mL, p < 0.001), but overall had only low-to-modest diagnostic accuracy (area under the curve [AUC]: 0.57, 95%CI 0.55–0.61) and were no independent predictor of functionally relevant CAD after multivariable adjustment (p = 0.068). Interleukin-6 concentrations had moderate-to-high accuracy in the prediction of cardiovascular death (AUC 0.75, 95%CI 0.69–0.82) and all-cause death (AUC 0.72, 95%CI 0.66–0.78) at 2-years, and remained a significant predictor after multivariable adjustment (p < 0.001). Compared to patients with interleukin-6 concentrations below the median (1.41 pg/mL), patients with concentrations above the median had a significantly higher cumulative incidence of cardiovascular death (1% vs. 4%, log-rank p < 0.001) and all-cause death (2% vs. 8%, log-rank p < 0.001) at 2 years. ConclusionInterleukin-6 concentrations are strong and independent predictors of cardiovascular death and all-cause death.

Eicosapantaenoic acid treatment based on the EPA/AA ratio in patients with coronary artery disease: follow-up data from the Tochigi Ryomo EPA/AA Trial in Coronary Artery Disease (TREAT-CAD) study.

Eicosapentaenoic acid (EPA) administration has been reported to decrease the incidence of cardiovascular events, and the serum EPA/arachidonic acid (AA) ratio has been identified as a potential new risk marker for coronary artery disease (CAD). The present study aimed to investigate the value of EPA treatment based on the EPA/AA ratio at baseline. We retrospectively analyzed clinical outcome data from 149 CAD patients with a baseline EPA/AA ratio ≤ 0.4 who had received purified EPA (EPA group) or not (no EPA group) and CAD patients with an EPA/AA ratio > 0.4 who had not received EPA (control group). The baseline EPA/AA ratios were similar in the EPA and no EPA groups and were significantly lower than those in the control group (P < 0.0001). The EPA/AA ratio significantly increased in the EPA group (P < 0.0001) and the no EPA group (P < 0.001) but not in the control group. The cumulative incidence of cardiovascular death tended to be lower in the EPA group (log-rank test: P = 0.07). Receiver operating characteristic curve analysis demonstrated that the cut-off value of the target EPA/AA ratio after EPA treatment for all-cause death was 1.23 (AUC = 0.85, P = 0.016). These results suggest that EPA treatment may improve the long-term prognosis in CAD patients with an EPA/AA ratio ≤ 0.4 and that an EPA/AA ratio > 1.2 may be an appropriate EPA treatment target value to reduce mortality.

Competing Risks of Cardiovascular Versus Noncardiovascular Death During Long-Term Follow-Up After Acute Coronary Syndromes.

BackgroundUnderstanding the relative risk of cardiovascular versus noncardiovascular death is important for designing clinical trials. These risks may differ depending on patient age, sex, and type of acute coronary syndrome (ACS).Methods and Results IMPROVE‐IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) was a randomized controlled trial of simvastatin plus either ezetimibe or placebo following stabilized ACS. Cause of death was adjudicated by an independent committee. We compared the cumulative incidence of cardiovascular and noncardiovascular death for patients with unstable angina/non‐ST‐segment elevation myocardial infarction (UA/NSTEMI) and ST‐segment elevation myocardial infarction (STEMI), in those <65 and ≥65 years old, and males and females, over 7 years of follow‐up. Of 18 131 patients, the presenting event was STEMI for 5190 (29%) and UA/NSTEMI for 12 941 (71%); 10 173 (56%) patients were <65 years old and 7971 (44%) were ≥65 years old at presentation. UA/NSTEMI patients were older than STEMI patients, with more cardiovascular and noncardiovascular risk factors. In STEMI patients, the cumulative incidence of cardiovascular death was higher for ∼4 years following the index event, after which noncardiovascular death predominated. In UA/NSTEMI patients, the cumulative incidence of cardiovascular death remained higher than noncardiovascular death over the full follow‐up period. Patients ≥65 years old and <65 years old had a higher incidence of cardiovascular death than noncardiovascular death over the entirety of follow‐up. Female patients had a higher incidence of cardiovascular death than noncardiovascular death for ∼6 years following the index event; male patients had a higher incidence of cardiovascular death than noncardiovascular death over the entirety of follow‐up.ConclusionsAmong post‐ACS patients enrolled in a long‐term clinical trial, the relative incidence of cardiovascular and noncardiovascular death differed based on type of ACS presentation and sex, but not age. These findings further delineate long‐term prognosis after ACS and should inform the design of future cardiovascular outcomes trials.

Impact of Low Diastolic Blood Pressure on Risk of Cardiovascular Death in Elderly Patients With Coronary Artery Disease After Revascularization - The CREDO-Kyoto Registry Cohort-1.

We investigated the effects of age and low diastolic blood pressure (DBP) on cardiovascular death in patients with coronary artery disease (CAD) after coronary revascularization. Stable, chronic CAD patients after coronary revascularization in the CREDO-Kyoto registry cohort-1 were allocated to the Young (≤64 years, n=2,619), Young-Old (65-74 years, n=2,932), and Old-Old (≥75 years, n=1,629) groups. Kaplan-Meier analysis showed that the crude cumulative incidence of cardiovascular death was higher in Young-Old patients with DBP <70 mmHg (P<0.001) and in Old-Old patients with DBP <60 mmHg (P=0.017), but not <70 mmHg (P=0.629), compared with each counterpart. Low DBP did not increase cardiovascular death in young patients. After adjustments with independent predictors, DBP <60 mmHg did not increase the cardiovascular death in the Old-Old group (HR=1.579 [95% CI, 0.944-2.642], P=0.082) and DBP <70 mmHg remained a predictor in the Young-Old group (HR=1.665 [1.094-2.532], P=0.017). On multivariate stepwise Cox proportional hazard regression analysis, independent predictors for cardiovascular death in low DBP patients were creatinine clearance (CCr; inversely), prior cerebrovascular disease, and aortic disease in the Young-Old group and CCr (inversely) and malignancy in the Old-Old group. DBP <60 mmHg was not an independent factor for predicting cardiovascular death in Old-Old revascularized CAD patients, whereas DBP <70 mmHg remained a predictor in the Young-Old. (Circ J 2016; 80: 1232-1241).

Polypharmacy and major adverse events in atrial fibrillation: observations from the AFFIRM trial.

Polypharmacy, as the use of five or more drugs, has commonly been associated with the elderly and multiple co-morbidities and related to impairment of clinical state and adverse outcomes, in general population. Limited data are available on the relationship between polypharmacy and adverse outcomes in atrial fibrillation (AF). We describe the prevalence of polypharmacy and AF, and its association with major adverse events, such as stroke and cardiovascular (CV) death. For this study, we analysed all AFFIRM Trial patients with complete pharmacological data. Polypharmacy was recorded in 40% of 4056 AF patients. The crude incidence of CV death was 3.45% patient-years among patients with polypharmacy, vs 1.65% patient-years without polypharmacy. Kaplan-Meier analysis showed that patients with polypharmacy had a higher cumulative incidence of CV death (p<0.001). Cox regression analysis demonstrated that female gender (p=0.038), diabetes mellitus (p=0.029), previous myocardial infarction (MI) (p=0.004), prior stroke (p=0.011) and polypharmacy (p=0.029) were independently associated with CV death. Polypharmacy was associated with an adjusted relative risk of 1.30 (95% CI 1.03-1.64) for CV death. A linear increase in the number of drugs was significantly associated with CV death. No significant association was found with stroke occurrence. Polypharmacy is highly prevalent in AF patients and associated with a worse clinical outcome, conferring 30% excess relative risk for CV death. Thus, polypharmacy may be a health status marker. Strategies to reduce inappropriate prescription and polypharmacy should be tested in prospective longitudinal studies of AF patients.

Prognostic value of a negative peak supine bicycle stress echocardiography with or without concomitant ischaemic stress electrocardiographic changes: a cohort study.

a negative peak supine bicycle exercise stress echocardiography (ESE) was shown to have a long-term favourable prognostic value. Data on the long-term prognosis of ischaemic electrocardiographic (ISECG) changes in the setting of a negative peak supine bicycle ESE are lacking. we evaluated the prognostic value of negative peak supine bicycle ESE with or without concomitant ISECG changes in a referral population evaluated for chest pain after an inconclusive first-line work-up including clinical evaluation and exercise ECG stress. from 2003 to 2010, patients who underwent a peak supine bicycle ESE and were deemed to be negative were evaluated. Two groups based on concomitant stress ECG tracing were analysed - those with normal stress ECG and those with ISECG changes. The primary endpoint was cumulative incidence of cardiovascular death, hospitalizations for acute coronary syndrome and coronary revascularizations. a total of 371 patients (mean age 59.1 ± 12.1 years, 49.9% women) were studied. Of those, 141 (38.0%) had concomitant ISECG changes. Mean follow-up was 3.46 ± 1.76 years. The primary endpoint occurred in 3.0% of patients, (2.2% in those with normal stress ECG, and in 4.3% with ISECG changes, p = 0.251); with unadjusted hazard ratio for primary endpoint of 2.04 (95%CI 0.62-6.69, p = 0.239) in patients with ISECG changes compared to those with normal stress ECG. in an outpatient population without known CAD evaluated for chest pain after inconclusive first-line work-up, a negative peak supine bicycle ESE confers an excellent prognosis regardless of the nature of concomitant stress ECG abnormalities.

Cardiovascular Death in Kidney Recipients Treated With Renin–Angiotensin System Blockers

Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are widely prescribed after kidney transplantation, but evidence for an improvement in outcomes is mixed. A recent trial demonstrated a significantly lower incidence of major cardiovascular events in ACEI-treated recipients. Collaborative Transplant Study data on cardiovascular death during years 2 to 10 after kidney transplantation in patients with a functioning graft were analyzed according to whether ACEI/ARB or other antihypertensive therapy (excluding diuretics) was administered at year 1. Of 39,251 transplants analyzed, 15,250 (38.9%) received ACEI/ARB and 24,001 (61.1%) received other antihypertensive therapy at year 1 after transplantation. The mean duration of follow-up was 5.8 years. During years 2 to 10 after transplantation, cardiovascular death occurred in 918 patients (cumulative incidence=4.7%) with a functioning graft. The rate of cardiovascular death was similar in patients who received ACEI/ARB therapy or other antihypertensive treatment overall and in subpopulations of patients who were considered by the transplant center to be at an increased cardiovascular risk, had no pretransplant risk factors, were aged 60 years and older, were treated for diabetes at year 1, or had serum creatinine of 130 μmol/L or higher at year 1. Multivariable Cox regression analysis confirmed that treatment with ACEI/ARB did not confer a beneficial effect beyond that conferred by other antihypertensive treatments on the cumulative incidence of cardiovascular death during years 2 to 10 (hazard ratio=1.1, P=0.24). This large-scale retrospective analysis of prospectively collected data shows that the rate of cardiovascular death in kidney transplant recipients receiving ACEI/ARB or other antihypertensive medications is virtually identical.

Survival and heart failure therapy in chronic dialysis patients with heart failure and reduced left ventricular ejection fraction: an observational retrospective study.

Aims We retrospectively followed 250 patients who started dialysis between 2005 and 2009 to clarify the prevalence, the prognosis and the prescribed heart failure treatment of systolic heart failure patients on dialysis.Methods and results This cohort was divided according to left ventricular ejection fraction (LVEF): group A with a reduced LVEF (≤ 45%, n = 45) versus group B with a preserved LVEF (> 45%, n = 205). Patients in group A had a signifi cantly worse survival after 12 and 24 months (68.9% and 55.5% vs. 87.3% and 73.0%, respectively, P= 0.0001). Hazard ratio for all-cause mortality was 2.70 (C.I. 95% 1.6 – 4.56, P= 0.0002). In the subgroup of patients with a LVEF < 30% the hazard ratio increased to 3.45 (C.I. 95% 1.71 – 6.94, P= 0.0005). The cumulative incidence of cardiovascular death was significantly higher in group A (hazard ratio: 4.78 (C.I. 95% 1.99 – 11.50, P= 0.0005), especially in the subgroup with a LVEF < 30%.In group A 71%, 31% and 9% of the patients received a beta blocker, an ACE inhibitor and an angiotensin-receptor blocker, respectively. Only 27% were treated with the combination of a beta blocker and a RAAS inhibitor, while 18% did not receive any heart failure therapy. Most patients only received a low dose of neurohormonal blockers (≤ 25% of the recommended daily dose). The use of these heart failure medications was not signifi cantly diff erent between group A and B.Conclusion After initiation of dialysis, patients with heart failure and reduced LVEF have a bad prognosis. Only a minority of these patients receive adequate specifi c heart failure treatment.

Low DBP may not be an independent risk for cardiovascular death in revascularized coronary artery disease patients

It remains controversial whether extremely low DBP is a risk for cardiovascular events in patients with coronary artery disease (CAD). Coronary revascularization therapy became prevalent in CAD patients. We sought to determine the impact of low DBP on cardiovascular events and to investigate the predicting factors in revascularized CAD patients. We subanalyzed 7180 stable, chronic CAD patients (median follow-up period 3.6 years) of 9877 patients undergoing first coronary artery bypass graft or percutaneous coronary intervention in the registry of the Coronary REvascularization Demonstrating Outcome study in Kyoto (CREDO-Kyoto). Kaplan-Meier analysis revealed that unadjusted cumulative incidence of cardiovascular death was greater in patients with preprocedural DBP of less than 70 mmHg than in those with DBP of at least 70 mmHg, whereas the cumulative incidences of nonfatal myocardial infarction (MI) and of stroke were similar between the two groups. Stepwise logistic regression analysis showed that estimated glomerular filtration ratio (inversely), pulse pressure, left ventricular ejection fraction of less than 0.40, history of heart failure, prior cerebrovascular disease, and prior MI were independent risks for cardiovascular death in patients with DBP of less than 70 mmHg. After adjustments for the independent risks, the cumulative hazard ratio for cardiovascular death did not differ between patients with DBP of less than 70 mmHg and those with DBP of at least 70 mmHg. Renal insufficiency, more advanced vascular damage, and left ventricular systolic dysfunction were significant factors accounting for increased cardiovascular death in revascularized CAD patients with DBP of less than 70 mmHg. It was suggested that after adjustments for these independent risks, low DBP may not be a significant risk for cardiovascular death in revascularized CAD patients.

Population-Based Study of Cardiovascular Mortality Among Patients With Prostate Cancer Treated With Radical External Beam Radiation Therapy With and Without Adjuvant Androgen Deprivation Therapy at the British Columbia Cancer Agency

There are conflicting studies of the impact of androgen deprivation therapy (ADT) on cardiovascular (CV) mortality among prostate cancer patients receiving curative intent external beam radiation therapy (EBRT). We assessed the impact of ADT on CV mortality in patients treated in British Columbia. Provincial pharmacy and radiotherapy databases were linked to the provincial cancer registry, and defined a cohort of patients treated with curative intent EBRT between 1998 and 2005. We determined the duration of ADT and the cumulative incidence of CV death. We compared death from CV disease with and without ADT, and by duration of ADT using competing risk analysis and Fine and Gray multivariant analysis. A total of 600 randomly selected patients were reviewed to determine baseline CV disease, CV risk factors, and Charlson Index. Of 5,948 prostate cancer patients treated with radical intent EBRT, of whom 1,933 were treated without ADT, 674 received ADT for ≤ 6 months and 3,341 received > 6 months of ADT. The cumulative CV mortality at 7 years was 2.6% (95% confidence interval [CI] 1.9-3.5%), 2.1% (95% CI = 1.2-3.5%), and 1.4 (95% CI = 1.0-2.0%) for patients with no ADT, ≤ 6 months of ADT, and >6 months of ADT, respectively (Gray's p = 0.002). Baseline CV disease and risk factors were more prevalent in the no-ADT group compared with the >6-month ADT group. This study demonstrated a lower CV mortality rate among patients treated with longer durations of ADT than those treated without ADT. These differences likely relate to selection of patients for ADT rather than effect of ADT itself.

A population-based study of cardiovascular (CV) mortality among patients with prostate cancer (PCa) treated with radical external beam radiation therapy (EBRT) with and without adjuvant androgen deprivation therapy (ADT) at a provincial cancer agency.

4656 Background: There are conflicting studies of the impact of ADT on CV mortality among PCa patients receiving curative intent EBRT. D’Amico et al suggested that men > 65 yrs are at increased risk of CV mortality with ADT. We assessed the impact of ADT on CV mortality in patients treated in British Columbia. Methods: Provincial pharmacy and radiotherapy databases were linked to the provincial cancer registry, and defined a cohort of patients treated with curative intent EBRT between 1998 and 2005. We determined the duration of ADT, and the cumulative incidence of CV death. We compared death from CV disease with and without ADT, and by duration of ADT using competing risk analysis and Fine and Gray multivariant analysis. 600 randomly selected patients were reviewed to determine baseline CV disease, CV risk factors, and Charlson Index. Results: We identified 5,948 PCa patients treated with radical intent EBRT, of which 1,933 were treated without ADT, 674 received ADT for ≤6 mo and 3,341 received > 6 mo of ADT. The cumulative CV mortality at 7 yrs was 2.6% [95%CI 1.9 to 3.5%], 2.1% [1.2 to 3.5%], and 1.4 [1.0 to 2.0%] for patients with no ADT, ≤ 6 mo NADT and > 6 mo ADT respectively (Gray's p=0.002). Baseline CVS disease and risk factors were more prevalent in the no ADT group compared to the > 6 month ADT group. Conclusions: This study demonstrated a lower CV mortality rate among patients treated with longer durations of ADT than those treated without ADT. These differences likely relate to selection of patients for ADT, rather than effect of ADT itself. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Ferring Pharma, sanofi-aventis AstraZeneca, Ferring Pharma, sanofi-aventis Abbott Laboratories