Higher Risk Of Cardiovascular Death Research Articles

Prognostic utility of rhythmic components in 24-h ambulatory blood pressure monitoring for the risk stratification of chronic kidney disease patients with cardiovascular co-morbidity

Chronic kidney disease (CKD) represents a significant global burden. Hypertension is a modifiable risk factor for rapid progression of CKD. We extend the risk stratification by introducing the non-parametric determination of rhythmic components in 24-h profiles of ambulatory blood pressure monitoring (ABPM) in the Chronic Renal Insufficiency Cohort (CRIC) and the African American Study for Kidney Disease and Hypertension (AASK) cohort using Cox proportional hazards models. We find that rhythmic profiling of BP through JTK_CYCLE analysis identifies subgroups of CRIC participants that were more likely to die due to cardiovascular causes. While our fully adjusted model shows a trend towards a significant association between absent cyclic components and cardiovascular death in the full CRIC cohort (HR: 1.71,95% CI: 0.99–2.97, p = 0.056), CRIC participants with a history of cardiovascular disease (CVD) and absent cyclic components in their BP profile had at any time a 3.4-times higher risk of cardiovascular death than CVD patients with cyclic components present in their BP profile (HR: 3.37, 95% CI: 1.45–7.87, p = 0.005). This increased risk was not explained by the dipping or non-dipping pattern in ABPM. Due to the large differences in patient characteristics, the results do not replicate in the AASK cohort. This study suggests rhythmic blood pressure components as a potential novel biomarker to unmask excess risk among CKD patients with prior cardiovascular disease.

CARDIOVASCULAR RISK AMONG MEN OF WORKING AGE WITH ARTERIAL HYPERTENSION DEPENDING ON THE ARTERIAL PRESSURE DIURNAL PROFILE

Aim: to investigate the relationship between cardiovascular risk (CVR) and different types of diurnal blood pressure (BP) profile among men of working age with arterial hypertension (AH).
 Materials and methods. The study included 83 men of working age (average age 48±2 years) with II stage, 2 and 3 degrees of AH. The risk of death due to cardiovascular diseases during the next 10 years was assessed using the SCORE scale. All patients underwent ambulatory BP monitoring (ABPM), according to the results of which the following diurnal BP profiles were identified: 23 (28%) patients – normal (optimal) level of nocturnal decrease in BP («dipper»; daily index (DI) 10-20%); 10 (12%) – excessive nocturnal lowering of BP («over-dipper»; DI >20%); 38 (46%) – insufficient nocturnal lowering of BP («non-dipper»; DI <10%); and 12 (14%) patients had an inverted diurnal curve («night-peaker»; DI <0%).
 Results and discussion. According to the SCORE scale, the CVR profile in «dipper» group (n=23) was as follows: low – 6 (26%) patients; moderate – 15 (65%); and high – 2 (9%). Among 10 patients of «over-dipper» group, 7 had low, 2 – moderate, and 1 – high CVR. In «non-dipper» group (n=38), there were 4 (11%) patients with low CVR, 10 (26%) with moderate, 14 (37%) with high, and 10 (26%) with very high CVR. At the same time, 7 out of 12 patients of «night-peaker» group showed very high CVR, 3 – high, and 2 – moderate (overall p<0,001). The frequency of patients with high CVR was higher in the pooled «non-dipper» and «night-peaker» group (pathological BP profile; n=50), as compared to the pooled «dipper» and «over-dipper» group (n=33): 34% vs. 9%, respectively. At the same time, the pooled «dipper» and «over-dipper» group was characterized by the higher frequency of patients with moderate (52%) and low CVR (39%), in contrast to the pooled «non-dipper» and «night-peaker» group (24% and 8%, respectively). Finally, all 17 patients with very high CVR had an abnormal diurnal BP profile (34% in the pooled «non-dipper» and «night-peaker» group) (overall p<0,001).
 Conclusions. It was established that, according to ABPM, 60% of men of working age with the AH of II stage, 2- and 3-degrees, had pathological BP profiles of the «non-dipper» and «night-peaker» types. Individuals diagnosed with nocturnal rise or insufficient diurnal BP decrease have a higher risk of cardiovascular death in the next 10 years according to SCORE. Patients with a «non-dipper» and «night-peaker» diurnal BP profiles require more aggressive drug therapy and re-examination with ABPM to control the normalization of the diurnal BP profile.

Marital Status Is a Prognostic Factor for Cardiovascular Mortality but Not a Prognostic Factor for Cancer Mortality in Siewert Type II Adenocarcinoma of the Esophagogastric Junction.

The impact of marital status on the prognosis of patients with Siewert type II adenocarcinoma of the esophagogatric junction (AEG) remained unclear. This study aimed to investigate the associations of marital status with cancer-specific death risk and cardiovascular death risk in Siewert type II AEG patients. Data for Siewert type II AEG patients were obtained from the Surveillance, Epidemiology, and End Results database from 2010 to 2015. A 1:1 propensity score matching (PSM) was applied to reduce inter-group bias between the married and unmarried groups. Kaplan-Meier analysis, a competing risk model and the Fine-Gray multivariable regression model were used to identify the prognostic value of marital status. In total, 1,623 subjects were included. After PSM, according to Fine-Gray multivariable regression analysis, there was no significant difference in the cumulative cancer-specific death rate between the married and the unmarried groups (hazard ratio (HR): 1.160, 95% confidence interval (CI): 0.994 - 1.354, P = 0.060). Patients in unmarried group had a higher cardiovascular death rate than patients in married group (HR: 3.066, 95% CI: 1.372 - 6.850, P = 0.006). Our study demonstrates that unmarried Siewert type II AEG patients are associated with higher cardiovascular death risk but not cancer-specific death risk compared with married patients.

Prognostic Significance of Elevated Left Ventricular Filling Pressures with Exercise: Insights from a Cohort of 14,338 Patients

Exercise echocardiography can assess for cardiovascular causes of dyspnea other than coronary artery disease. However, the prevalence and prognostic significance of elevated left ventricular (LV) filling pressures with exercise is understudied. We evaluated 14,338 patients referred for maximal symptom-limited treadmill echocardiography. In addition to assessment of LV regional wall motion abnormalities (RWMAs), we measured patients' early diastolic mitral inflow (E), septal mitral annulus relaxation (e'), and peak tricuspid regurgitation velocity before and immediately after exercise. Over a mean follow-up of 3.3±3.4years, patients with E/e' ≥15 with exercise (n=1,323; 9.2%) had lower exercise capacity (7.3±2.1 vs 9.1±2.4 metabolic equivalents, P<.0001) and were more likely to have resting or inducible RWMAs (38% vs 18%, P<.0001). Approximately 6% (n=837) had elevated LV filling pressures without RWMAs. Patients with a poststress E/e' ≥15 had a 2.71-fold increased mortality rate (2.28-3.21, P<.0001) compared with those with poststress E/e' ≤ 8. Those with an E/e' of 9 to 14, while at lower risk than the E/e' ≥15 cohort (hazard ratio [HR]= 0.58 [0.48-0.69]; P<.0001), had higher risk than if E/e' ≤8 (HR= 1.56 [1.37-1.78], P<.0001). On multivariable analysis, adjusting for age, sex, exercise capacity, LV ejection fraction, and presence of pulmonary hypertension with stress, patients with E/e' ≥15 had a 1.39-fold (95% CI, 1.18-1.65, P<.0001) increased risk of all-cause mortality compared with patients without elevated LV filling pressures. Compared with patients with E/e' ≤ 15 after exercise, patients with E/e' ≤15 at rest but elevated after exercise had a higher risk of cardiovascular death (HR= 8.99 [4.7-17.3], P<.0001). Patients with elevated LV filling pressures are at increased risk of death, irrespective of myocardial ischemia or LV systolic dysfunction. These findings support the routine incorporation of LV filling pressure assessment, both before and immediately following stress, into the evaluation of patients referred for exercise echocardiography.

Relevant adverse events and drug discontinuation of sacubitril/valsartan in a real-world Japanese cohort: REVIEW-HF registry

BackgroundThe characteristics, tolerability, and outcomes in patients with heart failure (HF) who are treated with sacubitril/valsartan remain unclear in Japan. MethodsWe conducted a nationwide multicenter study to evaluate the features and outcomes of patients newly prescribed sacubitril/valsartan for the management of HF. We analyzed adverse events (AEs) related to sacubitril/valsartan at 3 months, which were defined as hypotension, worsening renal function, hyperkalemia, and angioedema. Additionally, the association between AEs and outcomes was examined. ResultsAmong 993 patients, the mean age was 70 years and 291 (29.3 %) were female, and 22.8 % had left ventricular ejection fraction ≥50 %. Of them, 20.8 % had systolic blood pressure (sBP) <100 mmHg, and 19.5 % had estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2 at baseline, which were the populations excluded from the eligibility in landmark trials. AEs related to sacubitril/valsartan were observed in 22.5 % of the patients at 3 months. Overall, 22.6 % of patients discontinued sacubitril/valsartan, and hypotension was the most common event leading to drug discontinuation. After adjustment, patients who had worse HF symptoms (New York Heart Association III or IV), sBP <100 mmHg, and eGFR <30 ml/min/1.73 m2 were associated with a higher risk of AEs related to sacubitril/valsartan. Additionally, patients experiencing AEs had a higher risk of cardiovascular death or HF hospitalization than those who did not. ConclusionIn Japan, sacubitril/valsartan was also prescribed to patients not eligible for landmark trials, and AEs were observed at a relatively high rate from soon after treatment initiation. Physicians should closely monitor patients for these events, especially in patients anticipated to have a higher risk of AEs.

Short- and long-term outcomes of patients with minor stroke and nonvalvular atrial fibrillation

Background and purposeNonvalvular atrial fibrillation (NVAF) is a risk factor for stroke. This study was undertaken to determine the influence of NVAF on the mortality and recurrent stroke after a minor stroke event.MethodsData were derived from the Third China National Stroke Registry (CNSR-III) which enrolled 15,166 subjects during August 2015 through March 2018 in China. Patients with minor stroke (NIHSS ≤ 5) within 24 h after onset were included. Clinical outcomes including all-cause mortality, cardiovascular death, recurrent ischemic stroke, and recurrent hemorrhagic stroke were collected. The Cox proportional hazards models were used to determine the association between NVAF and clinical outcomes.ResultsA total of 4,753 patients were included in our study. Of them, 222 patients had NVAF (4.7%) (mean age, 71.1 years) and 4,531 patients were without AF (95.3%) (mean age, 61.4 years). NVAF was associated with 12-month cardiovascular mortality in both univariate (hazards ratio [HR], 4.13; 95% confidence interval [CI], 1.84 to 9.31; P < 0.001) and multivariate analyses (HR, 4.66; 95% CI, 1.79 to 12.15; P = 0.001). There was no difference in the in-hospital ischemic stroke recurrence rate between the two groups (HR, 0.45 [95% CI, 0.19 to 1.05] P = 0.07 at discharge). However, patients with NVAF had a lower rate of recurrent ischemic stroke at medium- (3 months and 6 months) and long-term (12 months) follow-up (HR, 0.33 [95% CI, 0.16 to 0.68] P = 0.003 at 3 months; 0.49 [95% CI, 0.27 to 0.89] P = 0.02 at 6 months; 0.55 [95% CI, 0.32 to 0.94] P = 0.03 at 12 months, respectively) compared with those without. There was no difference in all-cause mortality and hemorrhagic stroke between the two groups during follow-up.ConclusionsMinor stroke patients with NVAF were at higher risk of cardiovascular death but had a lower rate of recurrent ischemic stroke compared to those without during the subsequent year after stroke event. A more accurate stroke risk prediction model for NVAF is warranted for optimal patient care strategies.

Update on long-term cardiovascular risk after pre-eclampsia: a systematic review and meta-analysis.

There is a need for further studies on the cardiovascular risk of women experiencing pre-eclampsia (PE). To update the literature regarding the association between a history of PE and subsequent cardiovascular diseases, including cardiovascular death, coronary heart diseases, heart failure, and stroke, focusing on the trend in the effect size (ES) estimates over time. Following PRISMA guidelines, from inception to May 2023, we performed a systematic review of PubMed, MEDLINE, Scopus, and EMBASE. Randomized, cohort, or case-control studies in English were included if fulfiling the following criteria:(i) The association between PE and subsequent cardiovascular disease was adjusted for clinically relevant variables, (ii) the presence of a control group, and (iii) at least 1 year of follow-up. Pooled adjusted ESs and 95% confidence intervals (CIs) were used as effect estimates and calculated with a random-effect model. Twenty-two studies met the inclusion criteria. PE was associated with a higher risk of cardiovascular death (ES 2.08, 95% CI 1.70-2.54, I2 56%, P<0.00001), coronary artery diseases (ES 2.04, 95% CI 1.76-2.38, I2 87%, P<0.00001), heart failure (ES 2.47, 95% CI 1.89-3.22, I2 83%, P<0.00001), and stroke (ES 1.75, 95% CI 1.52-2.02, I2 72%, P<0.00001) after adjusting for potential confounders. This risk is evident in the first 1-to-3 years of follow-up and remains significant until 39 years of follow-up. Compared to women who experienced a normal pregnancy, those suffering from PE have about double the risk of lifetime cardiovascular disease.

Impact of balloon post-dilation on valve durability and long-term clinical outcomes after self-expanding transcatheter aortic valve implantation.

Balloon post-dilation (BPD) is a widely adopted strategy to optimize acute results of TAVI, with a positive impact on both paravalvular leak and mean gradients. On the other hand, the inflation of the balloon inside prosthetic leaflets may damage them increasing the risk of structural valve deterioration (SVD). Furthermore, the impact of BPD on long-term clinical outcomes and valve hemodynamics is yet unknown. To evaluate the impact of BPD on valve durability and long-term clinical outcomes in patients undergoing self-expanding transcatheter valve implantation (TAVI). Echocardiographic and clinical data from the ClinicalService (a nation-based data repository and medical care project) were analyzed. Patients were divided into two groups, those who underwent BPD after TAVI and those who did not. Coprimary endpoints were all-cause death and SVD. Cumulative incidence functions for SVD were estimated. Among 1835 patients included in the study, 417 (22.7%) underwent BPD and 1418 (77.3%) did not undergo BPD. No statistically significant differences at 6-year follow-up were found between groups in terms of all-cause mortality (HR: 1.05, 95% CI: 0.9-1.22; p = 0.557) and SVD (2.1% vs. 1.4%, p = 0.381). In addition, BPD did not predispose to higher risk of cardiovascular death, myocardial infarction, valve thrombosis, and endocarditis at 6-year follow-up. BPD following TAVI with a self-expanding prosthesis does not seem to be associated with an increased risk of adverse clinical outcomes or SVD at 6-year follow-up.

Soluble urokinase Plasminogen Activator Receptor (suPAR) is associated with educational attainment in patients with coronary artery disease

Abstract Background Biological mediators of adverse social determinants of health may include chronic low-grade inflammation. Elevation of circulating soluble urokinase Plasminogen Activator Receptor (suPAR) levels indicates activation of inflammatory and immune pathways and is associated with cardiovascular outcomes, independent of C-reactive protein (CRP) levels. Purpose We investigated whether the adverse impact of lower educational attainment on all-cause and cardiovascular mortality is mediated by elevated suPAR levels in patients with coronary artery disease (CAD). Methods In 3,164 patients undergoing coronary angiography, we investigated multivariable associations, including demographic characteristics, behavioral and clinical risk factors, between suPAR levels collected at the time of angiography and self-reported educational attainment, and assessed the relationship between lower educational level (defined as high school degree or less as highest educational qualification) and outcomes using Cox proportional hazard and Fine and Gray’s sub-distribution competing risk models. Mediation analyses were performed to assess the total effect of education on mortality, and the indirect effects through hs-CRP and suPAR on survival stratified by education using accelerated failure time models under exponential distribution. Results Mean age of the cohort was 64.5±11.9 years, with 32% women and 8.1±3.8 years follow-up. SuPAR levels were 9.0% [95% CI 6.3–11.8, p &amp;lt;0.0001] higher in patients achieving a lower (≤high school) compared to a higher (≥college) education after full covariate adjustment including hs-CRP levels. Lower educational attainment was associated with a higher risk of cardiovascular death (HR 1.39 [95% CI 1.15–1.68, p=0.0008]). After adjustment for demographic, clinical and behavioral covariates, and hs-CRP levels, this effect remained significant (HR 1.29 [95% CI 1.06–1.57, p=0.01]). However, after adjustment for suPAR levels, the effect of a lower educational level on cardiovascular mortality became insignificant. Values were similar for all-cause death. SuPAR levels mediated 49% and hs-CRP levels 17% of the association between lower educational attainment and cardiovascular mortality. Conclusion SuPAR importantly mediates the effects of lower educational attainment on mortality, indicating the importance of systemic inflammation and immune dysregulation as biologic mediators of adverse social determinants of health.Figure 1Central Illustration

Prognostic impact of ventricular tachycardia/fibrillation timing on cardio-vascular death in STEMI patients: 5 years of follow-up

Abstract Objectives Ventricular tachycardia (VT) and ventricular fibrillation (VF) are life-threatening arrhythmias that have negative impact on prognosis. This study investigated the relationship between the timing of VT or VF and long-term prognosis among ST-elevation myocardial infarction (STEMI) patients. Background It is unknown whether the timing of VT/VF occurrence affects the prognosis of patients with STEMI. Methods From 2001 to 2011 among 1621 STEMI patients (mean age 54,4±9,3 years) who participated in a prospective study, 221 (13.6%) had VT/VF during in-hospital stay. The mean time from STEMI symptoms onset was 4,5±0,1 h. 632 patients underwent TLT (39.0%), 267 (16.5%) - primary PCI. 772 (44,5%) patients did not undergo revascularization due to spontaneous recanalization or late admission. Patients with VT/VF were divided into two groups: early VT/VF - within 24 hour (h) of admission, 154 patients and late VT/VF - &amp;gt;24 h after admission, 67 patients. Patients have been monitored for 5 years of follow-up (FU). Cardiovascular (CV) death was the primary end-point. Results Patients with VT/VF were more likely to have cardiogenic shock, Killip Class II-III, AV block, and recurrent MI. Among STEMI patients the frequency of VT/VF occurrence was higher in patients with TLT – 19,0% and PTCA - 15,0% in compare to those without revascularization - 7,9%. However, the late VT/VF was 3.4 times less frequent among patients with TLT, 2.9 times - in PTCA, and twice less in patients without revascularization, compared to patients with early VT/VF. During FU long-term mortality has differed (Fig. 1). Kaplan-Mayer curves have significantly separated in late VT/VF group (p&amp;lt;0.01) during the first year (Fig. 2). Independent predictors of CV death in STEMI patients with late VT/VF were: higher Killip class (OR: 1.372, 95%CI 1.023-2.174, p&amp;lt;0.01), and higher peak CK-MB (OR: 1.031, 95% CI: 1.014-1.048, p&amp;lt;0.05). Conclusions VT and VF are frequent complications in STEMI and are powerful and independent predictors of 5-year survival. The timing of VT/VF occurrence had a peak during the first 24 h. However, patients with late VT/VF are at high risk of CV death in long-term FU and therefore require an individualized approach.

Beta-blockers after STEMI: prognostic impact and predictors of adherence, results from the real-world FAST-STEMI registry

Abstract Background The impact of beta-blocker therapy on cardiovascular outcomes after ST-elevation acute myocardial infarction (STEMI) is debated. Adherence to beta-blockers after acute myocardial infarction and effect on long term cardiovascular outcomes are also fields with significant knowledge gaps. Purpose To identify predictors of lower compliance to beta-blocker therapy and estimate its impact on cardiovascular outcomes and mortality during the first year of follow-up after the index event. Methods We evaluated real-world adherence to the most common cardiovascular drugs by comparing the number of tablets bought in pharmacies to the expected number of tablets needed at 1 year and at the final follow-up. A total of 6043 patients with STEMI were enrolled in the FAST-STEMI registry from 2012 to 2017 and followed up for 4.7±1.6 years. 299 patients with intraprocedural and intrahospital deaths were excluded. The main outcomes evaluated were all-cause death, cardiovascular death, myocardial infarction, major and minor bleeding events, and ischemic stroke. The best compliance cut-off was found by ROC curve analysis with Youden index; Kaplan Meier and Cox proportional hazard models were performed to evaluate cumulative event rates of mortality at follow-up. Predictors of lower adherence were evaluated in univariate and multivariate analyses with logistic regression. Results A total of 4992 patients with beta-blockers prescription at discharge were enrolled: mean age was 64±12.3 years old, 76% were male, mean ejection fraction was 49±8.8%. Mean adherence to beta-blockers was 95,8% (IQR 82.2-100). After univariate and multivariate analyses, age over 75 years old (OR 0.76, 95%CI 0.63-0.91) and previous coronary artery disease (OR 0.62, 95%CI 0.44-0.87) resulted as predictors of lower compliance, whereas concomitant ACEi/ARB prescription at discharge was a predictor of good adherence (OR 1.23, 95%CI 1.04-1.46). Adherence to beta-blockers higher than 65.68% (identified as best cut-off at Youden’s analysis) was related to a lower cardiovascular (0.65% vs 1.49%, p 0.009) and all-cause mortality (1.98% vs 4.48%, p &amp;lt;0.001). At multivariate analysis, adherence to beta-blockers was significantly associated with lower cardiovascular mortality (HR 0.40, 95%CI 0.20-0.81, p 0.01) as well as EF &amp;gt;50% (HR 0.30, 95%CI 0.14-0.63, p 0.002), while age over 75 years old (HR 4.72, 95%CI 2.23-9.98, p &amp;lt;0.001) and history of atrial fibrillation (HR 2.63, 95%CI 1.02-6.80, p 0.04) were associated with a higher risk of cardiovascular death. Finally, optimal adherence to beta-blockers did not reduce the number of myocardial infarctions, strokes, or bleeding events. Conclusions In our large real-world registry, optimal adherence to beta-blockers after STEMI was associated with a reduction in both cardiovascular and all-cause mortality. Older age and previous coronary artery disease resulted as predictors of poor compliance to beta-blocker therapy.Kaplan Meier on all-cause and CV deathMultivariate analysis on CV death

Soluble urokinase Plasminogen Activator Receptor (suPAR) mediates the effect of a lower education level on adverse outcomes in patients with coronary artery disease.

To investigate whether the adverse impact of lower educational attainment on mortality risk in patients with coronary artery disease (CAD) is mediated by the activation of inflammatory and immune pathways, estimated as elevated soluble urokinase plasminogen activator receptor levels. In 3164 patients undergoing coronary angiography, we investigated multivariable associations between suPAR and educational attainment and assessed the relationship between a lower educational level (defined as a high-school degree or less as the highest educational qualification) and outcomes using Cox proportional hazard and Fine and Gray's subdistribution competing risk models. The potential mediating effect through suPAR and high-sensitivity C-reactive protein (hs-CRP) was assessed using mediation analysis. A total of 1814 patients (57.3%) had achieved a higher (≥college) education level and 1350 patients (42.7%) a lower (≤high school) education level. Soluble urokinase plasminogen activator receptor levels were 9.0% [95% confidence interval (CI) 6.3-11.8, P ≤ 0.0001] higher in patients with lower educational qualifications than in those with higher educational qualifications after covariate adjustment. Lower educational attainment was associated with a higher risk of cardiovascular death after adjustment for demographic, clinical, and behavioural covariates, including CAD severity and heart failure history, medication use, and hs-CRP levels [hazard ratio 1.26 (95% CI 1.02-1.55, P = 0.03)]. However, after adjustment for suPAR levels, the effect of a lower educational level on cardiovascular death became insignificant. Values were similar for all-cause death. Soluble urokinase plasminogen activator receptor levels mediated 49% and hs-CRP levels 17% of the cardiovascular death risk attributable to lower educational attainment. Circulating suPAR levels importantly mediate the effects of lower educational attainment on mortality, indicating the importance of systemic inflammation and immune dysregulation as biologic mediators of adverse social determinants of health.

Vascular Disease Burden, Outcomes and Benefits with Empagliflozin in Heart Failure: Insights From the EMPEROR-Reduced Trial

Presence of ischemic heart disease impacts prognosis in patients affected by heart failure and reduced ejection fraction (HFrEF). It is not well known how the extent of vascular disease impacts prognosis and response to therapy in this setting. In this post hoc analysis of the EMPEROR-Reduced trial, outcomes, and the effect of empagliflozin, were assessed in study participants according to the extent (none vs. mono [1] vs. poly [≥2] vascular bed) of vascular disease. Vascular disease was defined as investigator-reported coronary artery disease (CAD), peripheral artery disease (PAD), and cerebrovascular disease at baseline. Cox proportional-hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). Incidence rates are presented per 100 person-years (py) of follow-up. Of the 3,730 study participants enrolled, 1324 (35.5%) had no, 1879 (50.4%) had mono, and 527 (14.1%) had poly-vascular disease. Participants with poly-vascular disease tended to be older, male, and with history of hypertension, diabetes, and smoking. In the placebo arm, a significant higher risk for cardiovascular death existed in those with poly-vascular disease (HR1.57, 95%CI 1.02, 2.44 compared to no vascular disease). In adjusted analysis, the benefit of empagliflozin on cardiovascular death or HF hospitalization, HF hospitalization, cardiovascular death, renal composite endpoint, estimated glomerular filtration slope changes, and health status scores, were seen across the three groups (interaction P>0.05 for all) but were attenuated in those with poly-vascular disease. Adverse events were higher in those with poly-vascular disease but there were no major differences noted between empagliflozin or placebo assignment in the three groups. In patients with HFrEF, the extent of vascular disease is associated with the risk for adverse cardiovascular outcomes. Empagliflozin offers cardiovascular and renal benefits in HFrEF across the extent of vascular disease, but this benefit is attenuated in those with poly-vascular disease.

Red blood cell count and risk of adverse outcomes in patients with mildly reduced left ventricular ejection fraction.

Anemia is associated with increased rates of heart failure (HF)-related mortality and hospitalization. No studies have focused on the association between the red blood cell (RBC) count and the prognosis of patients with HF with mildly reduced left ventricular ejection fraction (HFmrEF). We retrospectively analyzed the effect of the RBC count on outcome events in patients with HFmrEF. We investigated the association of the RBC count with outcome events in 1691 patients with HFmrEF (mean age: 68 years; 35% female) in Xiangtan Central Hospital. Using Cox proportional hazards models, the RBC count was assessed as both a continuous and categorical variable. During follow-up (median: 33 months), cardiovascular death occurred in 168 patients (114 men and 54 women). After adjusting for established risk factors, each 1.0 × 1012 cell/L increase in the RBC count was associated with a 28% lower risk of cardiovascular death in men and a 43% lower risk in women. Patients with low RBC counts had a 0.5-fold higher risk of cardiovascular death than those with normal RBC counts. The hazard ratio for men was 1.42 (95% confidence interval [CI]: 1.07-1.89), and the hazard ratio for women was 1.79 (95% CI: 1.20-2.67). The RBC count was not significantly associated with the composite endpoint of cardiovascular death and HF readmission (cardiovascular events) (p > .05). A decreased RBC count is associated with increased cardiovascular mortality in patients with HFmrEF. Correcting a low RBC count might potentially reduce the risk of cardiovascular death in patients with HFmrEF.

Persistent High Long-term Excess Mortality After Elective AAA Repair Especially in Women: A Large Population-based Study.

The aim of this time-trend analysis is to estimate long-term excess mortality and associated cardiovascular risk for abdominal aortic aneurysm (AAA) patients after elective repair while addressing the changes in AAA management and patient selection over time. Despite the intensification of endovascular aneurysm repair and cardiovascular risk management, Swedish population data suggest that AAA patients retain a persistently high long-term mortality after elective repair. The question is whether this reflects suboptimal treatment, a changing patient population over time, or a national phenomenon. Nationwide time-trend analysis including 40,730 patients (87% men) following elective AAA repair between 1995 and 2017. Three timeframes were compared, each reflecting changes in the use of endovascular aneurysm repair and intensification of cardiovascular risk management. Relative survival analyses were used to estimate disease-specific excess mortality. Competing risk of death analysis evaluated the risk of cardiovascular versus noncardiovascular death. Sensitivity analysis evaluated the impact of changes in patient selection over time. Short-term excess mortality significantly improved over time. Long-term excess mortality remained high with a doubled mortality risk for women (relative excess risk=1.87, 95% CI: 1.73-2.02). Excess mortality did not differ between age categories. The risk of cardiovascular versus noncardiovascular death remained similar over time, with a higher risk of cardiovascular death for women. Changes in patient population (ie, older and more comorbid patients in the latter period) marginally impacted excess mortality (2%). Despite changes in AAA care, patients retain a high long-term excess mortality after elective repair with a persistent high cardiovascular mortality risk. In this, a clear sex - but no age - disparity stands out.

Cardiovascular outcomes in breast cancer survivors: a systematic review and meta-analysis.

It is unclear whether the future risk of cardiovascular events in breast cancer (Bc) survivors is greater than in the general population. This meta-analysis quantifies the risk of cardiovascular disease development in Bc patients, compared to the risk in a general matched cancer-free population, and reports the incidence of cardiovascular events in patients with Bc. We searched PubMed, Scopus, and Web of Science databases (up to 23 March 2022) for observational studies and post hoc analyses of randomized controlled trials. Cardiovascular death, heart failure (HF), atrial fibrillation (AF), coronary artery disease (CAD), myocardial infarction (MI), and stroke were the individual endpoints for our meta-analysis. We pooled incidence rates (IRs) and risk in hazard ratios (HRs), using random-effects meta-analyses. Heterogeneity was reported through the I2 statistic, and publication bias was examined using funnel plots and Egger's test in the meta-analysis of risk. One hundred and forty-two studies were identified in total, 26 (836 301 patients) relevant to the relative risk and 116 (2 111 882 patients) relevant to IRs. Compared to matched cancer-free controls, Bc patients had higher risk for cardiovascular death within 5 years of cancer diagnosis [HR = 1.09; 95% confidence interval (CI): 1.07, 1.11], HF within 10 years (HR = 1.21; 95% CI: 1.1, 1.33), and AF within 3 years (HR = 1.13; 95% CI: 1.05, 1.21). The pooled IR for cardiovascular death was 1.73 (95% CI 1.18, 2.53), 4.44 (95% CI 3.33, 5.92) for HF, 4.29 (95% CI 3.09, 5.94) for CAD, 1.98 (95% CI 1.24, 3.16) for MI, 4.33 (95% CI 2.97, 6.30) for stroke of any type, and 2.64 (95% CI 2.97, 6.30) for ischaemic stroke. Breast cancer exposure was associated with the increased risk for cardiovascular death, HF, and AF. The pooled incidence for cardiovascular endpoints varied depending on population characteristics and endpoint studied. CRD42022298741.

258-OR: Type 2 Diabetes and Chronic Kidney Disease as Predictors of Cardiovascular Mortality in Patients with Established Cardiovascular Disease

This study aims to investigate the single and joint effects of T2DM and CKD on cardiovascular mortality in patients with established cardiovascular disease. We prospectively investigated 1755 patients with established cardiovascular disease, angiographically proven coronary artery disease (CAD) or sonographically proven peripheral artery disease (PAD), over 10.8±5.0 years. Cardiovascular death occurred more frequently in T2DM patients (n=568) than in nondiabetic subjects (30.4% vs 18.1%, p&amp;lt;0.001) and in patients with CKD (eGFR&amp;lt;60ml/min/1.73m2; n=300) than in those without CKD (35.7% vs 19.3%, p=0.001). When both T2DM and CKD were considered, 1015 subjects had neither T2DM nor CKD, 440 had T2DM but not CKD, 172 did not have diabetes but had CKD, and 128 had T2DM and CKD. Compared to the incidence of cardiovascular death among patients with neither T2DM nor CKD (15.8%), cardiovascular death occurred more frequently in patients with T2DM who did not have CKD (27.4%; p&amp;lt;0.001) as well as in nondiabetic patients with CKD (31.6%; p&amp;lt;0.001); the incidence of cardiovascular death was highest in patients with T2DM and CKD (41.3%; p&amp;lt;0.001), in whom it was higher than in those with T2DM but not CKD (p&amp;lt;0.001) or those without T2DM but with CKD (p=0.039); the incidence of cardiovascular death did not differ significantly between nondiabetic CKD patients and T2DM patients who did not have CKD (p=0.075). In Cox regression analysis, T2DM (HR 1.78 [1.43-2.21]; p&amp;lt;0.001) and CKD (HR 1.74 [1.36-2.23]; p&amp;lt;0.001) proved to be mutually independent predictors of cardiovascular mortality after multivariate adjustment for age, sex, BMI, history of smoking, hypertension, LDL-C and HDL-C. We conclude that T2DM and CKD in patients with established cardiovascular disease are mutually independent predictors of cardiovascular mortality. Cardiovascular disease patients with both CKD and T2DM are at an extremely high risk for cardiovascular death. Disclosure L. Sprenger: None. M. Maechler: None. A. Vonbank: None. B. Larcher: None. A. Mader: None. T. Plattner: None. A. Leiherer: None. A. Muendlein: None. H. Drexel: None. C.H. Saely: None.

Lower exercise capacity correlates with slower heart rate recovery in post-coronary artery bypass surgery patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Heart rate recovery (HRR) describes the ability of the autonomic nervous system changes from the sympathetic to the parasympathetic nervous system. The slower heart rate recovery means there is an autonomic dysfunction of the nervous system. Heart rate recovery has been known to be a predictor of mortality in patients undergoing exercise stress test. Patients with slow heart rate recovery have a higher risk of cardiovascular death. Decreased exercise capacity is also known to increase the risk of cardiovascular death. Purpose This study aims to determine the relationship between low exercise capacity and slow heart rate recovery. Methods Patients who underwent post-coronary artery bypass (CABG) surgery cardiovascular rehabilitation program at our national cardiovascular center in 2022 were enrolled in this study. We assessed heart rate recovery during the maximal exercise stress test, by subtracting from maximal heart rate during the exercise stress test with heart rate at the first and second minute after exercise stress test. We used predicted METs from Bruce protocols treadmill test time to determine each patient’s exercise capacity. Results There were 238 patients (age 58±7 years old, 89.9% male). The mean exercise capacity was 6.42±2.21 METs and the mean first and second-minute heart rate recovery was 14±11 and 26±15 beats per minute. Predicted exercise capacity had a significant positive weak correlation with first-minute heart rate recovery/HRR1 (r=0.279; p=0.000) and a significant positive moderate correlation with second-minute heart rate recovery/HRR2 (r=0.409; p=0.000) in post-CABG patients. We performed receiver operating characteristic analysis that showed the area under the curve for exercise capacity was 0.69 for HRR1 and 0.71 for HRR2, and found the exercise capacity cut-off was 5.5 METs . Patients with exercise capacity less than 5.5 METs were likely to have slower HRR1 (OR=4.4 (95% CI, 2.7 – 7.2) p=0.000) and slower HRR2 (OR=3.8 (95% CI, 2.4 – 6.0) p=0.000). Conclusions There is a correlation between low exercise capacity and slow heart rate recovery. Patients with lower exercise capacity were likely to have slower heart rate recovery in post-CABG patients.

Cardiovascular Protective Effects of NP-6A4, a Drug with the FDA Designation for Pediatric Cardiomyopathy, in Female Rats with Obesity and Pre-Diabetes.

Obese and pre-diabetic women have a higher risk for cardiovascular death than age-matched men with the same symptoms, and there are no effective treatments. We reported that obese and pre-diabetic female Zucker Diabetic Fatty (ZDF-F) rats recapitulate metabolic and cardiac pathology of young obese and pre-diabetic women and exhibit suppression of cardio-reparative AT2R. Here, we investigated whether NP-6A4, a new AT2R agonist with the FDA designation for pediatric cardiomyopathy, mitigate heart disease in ZDF-F rats by restoring AT2R expression. ZDF-F rats on a high-fat diet (to induce hyperglycemia) were treated with saline, NP-6A4 (10 mg/kg/day), or NP-6A4 + PD123319 (AT2R-specific antagonist, 5 mg/kg/day) for 4 weeks (n = 21). Cardiac functions, structure, and signaling were assessed by echocardiography, histology, immunohistochemistry, immunoblotting, and cardiac proteome analysis. NP-6A4 treatment attenuated cardiac dysfunction, microvascular damage (-625%) and cardiomyocyte hypertrophy (-263%), and increased capillary density (200%) and AT2R expression (240%) (p < 0.05). NP-6A4 activated a new 8-protein autophagy network and increased autophagy marker LC3-II but suppressed autophagy receptor p62 and autophagy inhibitor Rubicon. Co-treatment with AT2R antagonist PD123319 suppressed NP-6A4's protective effects, confirming that NP-6A4 acts through AT2R. NP-6A4-AT2R-induced cardioprotection was independent of changes in body weight, hyperglycemia, hyperinsulinemia, or blood pressure. Cardiac autophagy impairment underlies heart disease induced by obesity and pre-diabetes, and there are no drugs to re-activate autophagy. We propose that NP-6A4 can be an effective drug to reactivate cardiac autophagy and treat obesity- and pre-diabetes-induced heart disease, particularly for young and obese women.

Serum uric acid and left ventricular mass index independently predict cardiovascular mortality: The uric acid right for heart health (URRAH) project

A relationship between serum uric acid (SUA) and cardiovascular (CV) events has been documented in the Uric Acid Right for Heart Health (URRAH) study. Aimof this study was to investigate the association between SUA and left ventricular mass index (LVMI) and whether SUA and LVMI or their combination may predict the incidence of CV death. MethodsSubjects with echocardiographic measurement of LVMI included in the URRAH study (n=10733) were part of this analysis. LV hypertrophy (LVH) was defined as LVMI > 95 g/m2 in women and 115 g/m2 in men. ResultsA significant association between SUA and LVMI was observed in multiple regression analysis in men: beta 0,095, F 5.47, P< 0.001 and women: beta 0,069, F 4.36, P<0.001. During follow-up 319 CV deaths occurred. Kaplan–Meier curves showed a significantly poorer survival rate in subjects with higher SUA (> 5.6 mg/dl in men and 5.1 mg/dl in women) and LVH (log-rank chi-square 298.105; P<0.0001). At multivariate Cox regression analysis in women LVH alone and the combination of higher SUA and LVH but not hyperuricemia alone, were associated with a higher risk of CV death, while in men hyperuricemia without LVH, LVH without hyperuricemia and their combination were all associated with a higher incidence of CV death. ConclusionsOur findings demonstrate that SUA is independently associated with LVMI and suggest that the combination of hyperuricemia with LVH is an independent and powerful predictor for CV death both in men and women.