Incidence Rates Of Cardiovascular Events Research Articles

The transition of metabolic phenotypes and cardiovascular events: Panasonic cohort study 16.

The study objective was to investigate whether changes in metabolic phenotype affect the risk of cardiovascular events. All 117,589 participants were included in this retrospective cohort study. The metabolic phenotypes of the participants were assessed at two points (the second evaluation was set 2 years after the first evaluation), and the incidence rate of cardiovascular events was observed for 11 years. The main outcome was 3-point major adverse cardiac events (MACE), which comprises cardiovascular death, nonfatal coronary artery disease, and nonfatal stroke incidence. Of the participants, 2748 (2.3%) cases of 3-point MACE were identified during follow-up. The stable metabolically healthy obesity group had a higher risk of 3-point MACE than those with stable metabolically healthy nonobesity (MHNO). Additionally, the change from metabolically healthy obesity to MHNO for 2 years decreased the risk of 3-point MACE (hazard ratio [HR], 1.12: 95% CI: 0.84-1.47) to the same level as stable MHNO. However, the change from metabolically abnormal nonobesity and metabolically abnormal obesity to MHNO for 2 years maintained a higher risk of 3-point MACE (HR, 1.66 [95% CI: 1.36-2.01]; HR, 1.91 [95% CI: 1.22-2.81]) than those with stable MHNO. Change in metabolic phenotype is associated with incident 3-point MACE.

Immune Checkpoint Inhibitors and the Risk of Cardiovascular Adverse Events: A Pooled Clinical Trial Database Analysis

Introduction Immune checkpoint inhibitors (ICIs) are a highly effective class of cancer immunotherapy, but their use has been limited by immune-related adverse events (irAEs) affecting various organ systems. Recent real-world studies have shown higher incidence rates of cardiovascular (CV) events in patients with cancer who are treated with ICIs compared to those treated with conventional chemotherapy (Laenens et al, J Clin Oncol 2022). Studies suggest that the underlying mechanism involves a pro-inflammatory response causing unintended vascular compromise, but there have been limited data on ICI-related cardiotoxicity across pooled datasets. Given that ICIs have been applied to lung cancer treatment in recent years, we use it as an example indication to study clinical trial (CT) patients with advanced non-small cell lung cancer (aNSCLC) randomized to either a first-line (1L) ICI-containing regimen or to 1L chemotherapy alone (chemo) to evaluate for potential differential rates of CV events. Methods We pooled patient-level, phase 3 CT data on aNSCLC patients treated with ICI or chemo from the Medidata Enterprise Data Store. Treatment assignment was the main variable of interest. The primary outcome was a composite CV event (acute coronary syndrome, heart failure, stroke, transient ischemic attack), occurring between the start of study treatment (index date) and 30 days following the last dose of study treatment. Incidence rates and the relative hazard of a CV event by treatment assignment were estimated. Additionally, the risk of CV event with non-CV death treated as a competing risk was estimated using the Fine-Gray model. In a post-hoc subgroup analysis we explored the impact of treatment assignment on overall survival (OS) among patients with and without baseline vascular disease. OS was defined as the time from the index date until the date of death (all-cause). Patients alive at the end of CT follow-up were censored. Results A total of 1862 patients were included in this analysis, with 1128 (60.6%) randomized to ICI and 734 (39.4%) to chemo. Baseline demographics and comorbidities were balanced across treatment groups. Forty-six (2.5%) patients experienced at least 1 CV event. The incidence rate of CV events was 2.48 times (95% CI: 1.10, 6.57) higher among patients treated with ICI compared to chemo. The unadjusted hazard of composite CV event, estimated using Kaplan-Meier, differed significantly by treatment assignment (p= 0.008) ( Figure 1). After adjusting for baseline demographics and comorbidities, the hazard of a composite CV event remained higher for patients treated with ICI compared to chemo (aHR 2.68, 95% CI: 1.19-6.06) ( Table 1). Baseline vascular disease history (N=359; 19.3%) was also associated with an increased hazard of a CV event (aHR: 2.40; 95% CI: 1.25-4.60). Similar results were found in the competing risk analysis. In the subgroup analysis, patients without baseline vascular disease history had a significant OS benefit from an ICI compared to chemo (aHR 0.84, 95% CI: 0.75-0.95), whereas patients with baseline vascular disease did not (aHR 1.00, 95% CI: 0.78-1.27). Conclusion Though ICIs enhance the body's immune responses against cancer, it is important to study the associated effect of irAEs on off-target tissues. These analyses of historical CT data suggest a positive association between 1L treatment of aNSCLC with ICI and subsequent composite CV events compared with chemo alone. Given the high prevalence of morbidity among patients with lung cancer, the use of concomitant cardioprotective therapies may be an important consideration when treating cancer populations with ICIs. Pooling CT data increases the power to detect clinically important differences in rare toxicities and may inform future research and patient-physician decision-making regarding the suitability of ICI use in aNSCLC treatment. Furthermore, this research highlights the potential clinical utility of drug repurposing: expanding the use of drugs approved to treat CV events and exploring their use in patients with vascular disease who are also being treated with ICIs. As cell-mediated immune responses play a key role in the potential CV effects of ICI treatments, future studies are needed to define the underlying mechanisms of ICI-related dysregulation of the immune system to better monitor patients and improve clinical outcomes in the context of immunotherapy for aNSCLC and other cancer types.

Vertebral Tortuosity Is Associated With Increased Rate of Cardiovascular Events in Vascular Ehlers-Danlos Syndrome.

Background Arterial tortuosity is associated with adverse events in Marfan and Loeys-Dietz syndromes but remains understudied in Vascular Ehlers-Danlos syndrome. Methods and Results Subjects with a pathogenic COL3A1 variant diagnosed at age <50 years were included from 2 institutions and the GenTAC Registry (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions). Height-adjusted vertebral artery tortuosity index (VTI-h) using magnetic resonance or computed tomography angiography was calculated. Associations between VTI-h and outcomes of (1) cardiovascular events (arterial dissection/rupture, aneurysm requiring intervention, stroke), or (2) hollow organ collapse/rupture at age <50 years were evaluated using receiver operator curve analysis (using outcome by age 30 years) and mixed-effects Poisson regression for incidence rate ratios. Of 65 subjects (54% male), median VTI-h was 12 (interquartile range, 8-16). Variants were missense in 46%, splice site in 31%, and null/gene deletion in 14%. Thirty-two subjects (49%) had 59 events, including 28 dissections, 5 arterial ruptures, 4 aneurysms requiring intervention, 4 strokes, 11 hollow organ ruptures, and 7 pneumothoraces. Receiver operator curve analysis suggested optimal discrimination at VTI-h ≥15.5 for cardiovascular events (sensitivity 70%, specificity 76%) and no association with noncardiovascular events (area under the curve, 0.49 [95% CI, 0.22-0.78]). By multivariable analysis, older age was associated with increased cardiovascular event rate while VTI-h ≥15.5 was not (incidence rate ratios, 1.79 [95% CI, 0.76-4.24], P=0.185). However, VTI-h ≥15.5 was associated with events among those with high-risk variants <40 years (incidence rate ratios, 4.14 [95% CI, 1.13-15.10], P=0.032), suggesting effect modification by genotype and age. Conclusions Increased arterial tortuosity is associated with a higher incidence rate of cardiovascular events in Vascular Ehlers-Danlos syndrome. Vertebral tortuosity index may be a useful biomarker for prognosis when evaluated in conjunction with genotype and age.

O-011 Cardiovascular morbidity and mortality in women with PCOS: a cohort study of 75142 participants from the UK biobank

Abstract Study question Are women with PCOS at an increased risk of cardiovascular mortality and morbidity? Summary answer Although PCOS is strongly associated with cardiovascular risk factors, it does not increase the risk of cardiovascular morbidity and mortality in women aged 40-60 years. What is known already PCOS is one the commonest endocrinopathies in women of reproductive age characterised by anovulation, hyperandrogenism and polycystic ovaries in ultrasound surveillance. The prevalence of PCOS has been quoted 8 to13% of women in the UK, however, up to 70% of the cases may be undiagnosed. Women with PCOS are at increased risk of developing adverse cardiometabolic outcomes including insulin resistance, type 2 diabetes (T2DM), metabolic syndrome, hypertension and dyslipidaemia. Those unfavourable risk factors would place women with PCOS at an increased risk for cardiovascular mortality and morbidity, however, the evidence from epidemiological studies are so far heterogenous with conflicting results. Study design, size, duration We conducted a cohort study including a total of 75142 participants from the UK biobank, of whom 15747 had PCOS. Women were followed up for 11.1 years in average. Participants/materials, setting, methods The primary outcome was morbidity and mortality from ischemic heart disease and stroke. We constructed Cox regression analysis adjusted for confounders and risk factors to quantify the risk of cardiovascular morbidity and mortality in women with PCOS. Main results and the role of chance The incidence rate of cardiovascular events was 1.92/1000 person years in the PCOS population and 1.90/1000 person years in women without PCOS. PCOS was associated with a higher risk of obesity (OR 1.63, 95% CI 1.56-1.70), hypertension (OR 1.18, 95% CI 1.13-1.23) and type 2 diabetes (OR 1.44, 95% CI 1.31-1.58). In the adjusted cox regression model, PCOS doesn’t increase the risk of CVD morbidity and mortality (HR 0.89, 95% CI 0.78-1.01), however, the cumulative hazard risk in women over 60 years old with a history of PCOS was greater compared to women without PCOS. Limitations, reasons for caution The low response rate (5.5%) to the UK biobank recruitment introduces a healthy responder bias which may limit the representation of the population. PCOS was both self-reported and assessed by clinical and biochemical features and other variables were also self-reported, hence reporting bias cannot be excluded. Wider implications of the findings The strong association of PCOS with cardiometabolic risk factors and that the CVD morbidity/mortality risk becomes comparable with that of women without PCOS after correcting for these factors, highlights the need to strengthen public health strategies for surveillance, lifestyle interventions and prompt treatment of those co-morbidities in women with PCOS. Trial registration number Not applicable

Modifiability of Composite Cardiovascular Risk Associated With Chronic Kidney Disease in Type 2 Diabetes With Finerenone

It is currently unclear whether chronic kidney disease (CKD)-associated cardiovascular risk in type 2 diabetes (T2D) is modifiable. To examine whether cardiovascular risk can be modified with finerenone in patients with T2D and CKD. Incidence rates from Finerenone in Chronic Kidney Disease and Type 2 Diabetes: Combined FIDELIO-DKD and FIGARO-DKD Trial Programme Analysis (FIDELITY), a pooled analysis of 2 phase 3 trials (including patients with CKD and T2D randomly assigned to receive finerenone or placebo) were combined with National Health and Nutrition Examination Survey data to simulate the number of composite cardiovascular events that may be prevented per year with finerenone at a population level. Data were analyzed over 4 years of consecutive National Health and Nutrition Examination Survey data cycles (2015-2016 and 2017-2018). Incidence rates of cardiovascular events (composite of cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, or hospitalization for heart failure) were estimated over a median of 3.0 years by estimated glomerular filtration rate (eGFR) and albuminuria categories. The outcome was analyzed using Cox proportional hazards models stratified by study, region, eGFR and albuminuria categories at screening, and cardiovascular disease history. This subanalysis included a total of 13 026 participants (mean [SD] age, 64.8 [9.5] years; 9088 male [69.8%]). Lower eGFR and higher albuminuria were associated with higher incidences of cardiovascular events. For recipients in the placebo group with an eGFR of 90 or greater, incidence rates per 100 patient-years were 2.38 (95% CI, 1.03-4.29) in those with a urine albumin to creatinine ratio (UACR) less than 300 mg/g and 3.78 (95% CI, 2.91-4.75) in those with UACR of 300 mg/g or greater. In those with eGFR less than 30, incidence rates increased to 6.54 (95% CI, 4.19-9.40) vs 8.74 (95% CI, 6.78-10.93), respectively. In both continuous and categorical models, finerenone was associated with a reduction in composite cardiovascular risk (hazard ratio, 0.86; 95% CI, 0.78-0.95; P = .002) irrespective of eGFR and UACR (P value for interaction = .66). In 6.4 million treatment-eligible individuals (95% CI, 5.4-7.4 million), 1 year of finerenone treatment was simulated to prevent 38 359 cardiovascular events (95% CI, 31 741-44 852), including approximately 14 000 hospitalizations for heart failure, with 66% (25 357 of 38 360) prevented in patients with eGFR of 60 or greater. Results of this subanalysis of the FIDELITY analysis suggest that CKD-associated composite cardiovascular risk may be modifiable with finerenone treatment in patients with T2D, those with eGFR of 25 or higher, and those with UACR of 30 mg/g or greater. UACR screening to identify patients with T2D and albuminuria with eGFR of 60 or greater may provide significant opportunities for population benefits.

Correlation between Count Score and Cardiovascular Events in Maintenance Hemodialysis Patients

Purpose: Evaluating the nutritional status of patients with Maintenance Hemodialysis (MHD) based on CONUT score to explore its relationship with Cardiovascular Disease (CVD) in MHD patients. Methods: Baseline data of new-coming MHD patients hospital hemodialysis center of our hospital undergoing hemodialysis treatment for the first time from January 1, 2014 to June 30, 2020 was collected. Cardiovascular events were used as the end point. Patients were divided into three groups according to CONUT score: normal nutrition group (CONUT score 0-1), mild malnutrition group (CONUT score 2-4) and moderate to severe malnutrition group (CONUT score ≥5), and the differences of clinical data and prognosis among the three groups were compared. The risk factors of cardiovascular events in MHD patients were determined by Logistic regression analysis, and the predictive ability of the risk factors was observed with Receiver Operating Characteristic (ROC) curve. Results: A total of 424 MHD patients were included. According to the CONUT score, 31 (7.3%) patients were in the normal nutrition group, 160 (37.7%) patients in the mild malnutrition group, and 233 (55.0%) patients in the moderate to severe malnutrition group. A total of 159 patients had cardiovascular events, including 3 cases (9.7%) in the normal nutrition group, 38 cases (23.8%) in the mild malnutrition group, and 118 cases (50.6%) in the moderate to severe malnutrition group. The worse the nutritional status of patients is, the higher the incidence rate of cardiovascular events is (P&lt;0.05). Logistic regression analysis showed that CONUT score and age were independently correlated with cardiovascular events in MHD patients (P&lt;0.05). ROC curve analysis showed that CONUT score and age predicted cardiovascular events in MHD patients with areas under the curve were 0.683 (95% CI: 0.632-0.735, P&lt;0.001) and 0.702 (95% CI: 0.702), respectively. 0.652 -- 0.753, P&lt;0.001), the optimal cut-off points were 4.5 (≥5 in combination) and 68.5, the sensitivity were 74.2% and 49.1%, and the specificity was 56.6% and 81.1%, respectively. Conclusion: There is a certain correlation between CONUT score the happening of cardiovascular events and MHD patients.

Sex-specific associations of myocardial perfusion imaging with outcomes in patients with suspected chronic coronary syndrome

BackgroundMyocardial perfusion scintigraphy (MPS) is an established diagnostic technique for inducible ischemia in patients with suspected chronic coronary syndrome (CCS). Some MPS findings, most notably an ischemia extent>10% of the left ventricle (LV), hold prognostic significance and support maximization of anti-ischemic treatment. We aimed to assess sex-specific associations of MPS findings with cardiovascular (CV) events in a population at high risk of CCS. MethodsIn a prospective cohort study, 1,229 consecutive patients (age 70 ± 9.5 years, 73.5% males) without known CCS were referred to stress-rest MPS. All patients were followed for a median of 4.6 years for CV events. ResultsMen and women had comparable risk profiles and incidence rates of CV events (6.6% vs. 4.6% respectively, P = 0.186). A summed stress score (SSS) > 7 was associated with the primary endpoint, including CV death and/or nonfatal myocardial infarction (MI) (adjusted hazard ratio [HR], 3.13; 95% confidence interval [CI], 1.79-5.46; P = 0.001), all-cause mortality (HR, 3.01; 95% CI, 1.31-6.93; P = 0.01), and incidence of late revascularization (HR, 1.84; 95% CI, 1.22-2.78; P = 0.004) in men but not women. A summed difference score (SDS) > 6 was related to a higher rate of the primary endpoint only in men (adjusted HR, 1.97; 95% CI, 1.18-3.30; P = 0.009). ConclusionsAmong patients undergoing a diagnostic workup for suspected CCS, stress perfusion and reversible ischemia abnormalities may independently predict worse survival and more CV events in men. However, the obtained results indicated the need for sex-specific cutoffs to refine risk stratification and assist in clinical decisions on anti-ischemic therapy beyond coronary artery anatomy.

Rates of cardiovascular events among patients with moderate-to-severe atopic dermatitis in an integrated health care system: A retrospective cohort study.

Patients with versus without atopic dermatitis may have a greater risk of cardiovascular events, and the risk increases with severity of atopic dermatitis. The incidence of cardiovascular events in the population of patients with moderate-to-severe atopic dermatitis is largely unknown. This retrospective study evaluates incidence rates of cardiovascular events in patients aged ≥12 years with moderate-to-severe atopic dermatitis in a cohort of Kaiser Permanente Northern California health care system members without recognized risk factors for adverse events. Patients with moderate-to-severe atopic dermatitis, as defined by dermatologist-rendered code and prescription history between 2007 and 2018, were included. Major adverse cardiovascular events, venous thrombotic events, deep vein thrombosis, and pulmonary embolisms were identified via International Classification of Diseases codes. Stratification variables included age, sex, race, smoking history, and diabetes. Incidence rates per 1000 person-years were calculated by the number of patients with an incident event divided by the total person-years of observation. Among 8197 patients with moderate-to-severe atopic dermatitis, incidence rates per 1000 person-years (95% confidence interval) for major adverse cardiovascular events, venous thrombotic events, deep vein thrombosis, and pulmonary embolism were: 2.6 (2.1-3.2), 2.0 (1.5-2.5), 1.6 (1.2-2.1), and 0.7 (0.5-1.0), respectively. Incidence rates for all events were higher for older versus younger patients, patients with versus without diabetes, former smokers versus patients who had never smoked, and men versus women, except for pulmonary embolisms, which were higher in women. This study estimated the incidence of cardiovascular events in patients with moderate-to-severe atopic dermatitis and provides valuable information for clinicians.

In patients with type 2 diabetes chronic kidney disease is a modifiable cardiovascular risk factor

Abstract Background/Introduction Chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) is associated with an increased risk of cardiovascular (CV) events. The modifiability of CKD-associated CV risk in patients with T2D across a spectrum of CKD stages remains unknown. Purpose To test whether CKD, as defined jointly by estimated glomerular filtration rate (eGFR) and albuminuria (urine albumin-to-creatinine ratio [UACR]), is a modifiable CV risk factor in patients with T2D. Furthermore, to estimate the population-wide reduction in first CV events in the US if all eligible patients were treated with finerenone. Methods We estimated the incidence rates of CV events (composite of CV death, non-fatal stroke, non-fatal myocardial infarction, or hospitalisation for heart failure) over a median follow-up of 3.0 years in 13,026 patients with CKD and T2D, treated with finerenone or placebo, in a joint analysis by eGFR and UACR categories. Patients were from FIDELITY, a prespecified pooled analysis of two phase III trials, and had an eGFR ≥25 ml/min/1.73 m2 and UACR 30–5000 mg/g at screening.The potential impact of finerenone treatment on the US population was evaluated by simulating the number of first CV events that could be prevented per year with finerenone, using incidence rates from FIDELITY and prevalence rates of CKD in patients with T2D from the National Health and Nutrition Examination Survey (NHANES). Results Lower eGFR and higher UACR categories were associated with higher incidences of CV events in finerenone and placebo recipients (Figure). Finerenone reduced CV risk versus placebo (hazard ratio 0.86; 95% CI 0.78–0.95; p=0.0018) without evidence of moderation of risk reduction by combined eGFR and UACR categories (p interaction = 0.66; Figure 1). Using NHANES, a total of 6.4 million treatment-eligible individuals with CKD and T2D were identified; 75% had CKD with an eGFR ≥60 ml/min/1.73 m2 and 25% had CKD with an eGFR &amp;lt;60 ml/min/1.73 m2. Simulations using this NHANES population projected that 1 year of finerenone treatment could prevent 38,359 CV events in US patients with CKD and T2D, with 66% of events prevented in patients with eGFR ≥60 ml/min/1.73 m2. Conclusions Higher albuminuria and lower eGFR are associated with increased CV risk in patients with T2D. Across a range of eGFR and albuminuria categories, CV risk is modifiable. Therefore, CKD is a modifiable CV risk factor in part mediated by mineralocorticoid receptor overactivation. UACR screening to identify patients with T2D and albuminuria with an eGFR ≥60 ml/min/1.73 m2 is likely to provide a significant opportunity for population benefits. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer AG

Clinical consequences of the lipid-lowering treatment in patients with acute coronary syndrome: real-world retrospective study (LipidACS study)

Abstract Background The reduction of low-density lipoprotein cholesterol (LDLc) levels is Key for improving the prognosis of patiens with acute coronary syndrome (ACS). Purpose To estimate the clinical characteristics and treatments of patients with a first episode of ACS in real world in a large database in Spain. Methods An observational and retrospective study was carried out based on electronic medical records of primary care centers and hospitals including 969.587 spanish patients aged &amp;gt;18 years.From these, we selected the ones with a first episode of ACS between 01/07/2016 and 30/06/2018, with a follow-up period of 18 months. Patients were divided according to the intensity of their lipid-lowering treatments: low, moderate, high (high intensity statin/moderate plus ezetimibe), very high (high intensity statin plus ezetimibe) and extreme (IPCSK added) and those on treatment with lipid-lowering drugs other than statins. The incidence of new cardiovascular events, the reduction of LDLc levels, the persistence rates at 9 and 18 months, and the mortality rates were estimated. The concomitant treatments prescribed at the start of the study were registered. Results A first episode of ACS was detected in 7,150 patients (mean age: 70 years [SD: 9.6]; males: 62.2%). The intensity of their lipid-lowering treatments: low [n=172 (2.4%)], moderate [n=370 (5.2%)], high [n=3,751 (52.5%)], very high [n=2,457 (34.4%)], extreme [n=67 (0.9%)])and non-statins lipid-lowering treatments (n=333 [4.7%]). Patients with lipid-lowering treatments other than statins had the highest incidence rate of cardiovascular events (33.0%), followed by those on treatment with low intensity treatments (32.0%): acute myocardial infarction and angina were the most frequent cardiovascular events. The deepest reductions of LDLc levels at 18 months were reported in patients with extreme intensity and very-high intensity treatments (−60.5 mg/dL [42.9%] and −31.6 mg/dL [24.3%], respectively). The persistence rates at 9 and 18 months were higher in patients with extreme intensity and very high intensity lipid-lowering treatments. The highest mortality rate was observed in patients with lipid-lowering treatments other than statins (12.6%), with the median time to death being 221 days (P25–P75: 116–327). The lowest mortality rate was registered in patients with extreme intensity lipid-lowering treatments, who showed a median time to death of 405 days (P25–P75: 396–0).Overall, referral to Cardiac Rehabilitation in ACS is less than 20% in Spain. Conclusion Patients with ACS who received lipid-lowering treatments other than statins and low intensity treatments had the highest incidence of cardiovascular events and mortality rates.The reduction of LDLc levels increased with the intensity of the lipid-lowering treatments, which may lead to a reduced risk of cardiovascular events and death. More referral to Cardiac Rehabilitation could also improve these results Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): SANOFI

COST-EFFECTIVENESS OF INTENSIVE VERSUS STANDARD BLOOD-PRESSURE CONTROL IN OLDER PATIENTS WITH HYPERTENSION

Objective: In the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial, Chinese patients aged 60 to 80 years who received intensive systolic blood-pressure control (target, 110 to 130 mmHg) had a significantly lower incidence rate of cardiovascular events than did those who received standard control (target 130 to 150 mmHg). Based on these data, we aimed to examine the lifetime cost-effectiveness of intensive versus standard blood-pressure control from the different healthcare providers’ perspectives. Design and method: A microsimulation model was employed to apply STEP treatment effects and medical costs and utility from national sources or published data to a hypothetical cohort of STEP-eligible patients in China. Incremental cost-effectiveness ratio (ICER) against willing-to-pay threshold was used to evaluate whether intensive versus standard blood-pressure control was a cost-effective option. A series of sensitivity, subgroup, and scenario analyses in other countries (the US and UK) were performed to account for the generalisability and uncertainties arising from study assumptions and parameters. Results: The ICER values of intensive versus standard blood-pressure control were approximate ¥ 48,000, $32,300, £10,055 per QALY gained from the perspective of healthcare providers in China, the US and the UK. Simulation results indicated that intensive treatment would be cost-effective (54.6% and 70.1% below the willing-to-pay thresholds of ¥ 80,000 and ¥240,000). The scenario analyses presented that intensive treatment would be cost-effective in the US and UK settings (63.9% and 80.4% below the willing-to-pay thresholds of $50,000 and $150,000 in the US; 75% and 82.1% below the willing-to-pay thresholds of £30,000 and £90,000 in the UK) Conclusions: In this simulation study, intensive blood-pressure control in the older Chinese population produced fewer cardiovascular events and acceptable costs per QALY gained, commonly below the willing-to-pay threshold. Given the STEP treatment effects in other populations, the cost-effectiveness of intensive blood-pressure control in older patients was likely consistent across different countries.

Research on the Correlation between Plasma BNP and the Condition and Prognosis of Chronic Heart Failure

This study aimed to analyze the correlation between the level of brain natriuretic peptide (BNP) and the condition and prognosis of chronic heart failure (CHF). For this purpose, between January 2017 and July 2020, we recruited a total of 120 CHF patients who were treated in Cangzhou Central Hospital into this study, consisting of 40 patients in NYHA II, 40 in NYHA III and 40 in NYHA IV, and simultaneously, 40 subjects with normal heart function were enrolled into the control group. General data were collected from the patients and subjects, and laboratory tests regarding the BNP level, LVEDD and LVEF were carried out. Correlation between plasma level of BNP and the evaluation of condition and prognosis of CHF was also analyzed. For further evaluation, the expression of BNP gene expression was considered in the femoral blood of participants by the Real-time PCR technique. The results showed that comparison over the clinical data of subjects among these groups showed no significant difference (P &gt; 0.05). In the research group, the averages of LVEDD and BNP in plasma were (58.53±3.75) mm and (5089.86±22.39) pg/mL, significantly higher than those in the control group, while the LVEF was (45.66±3.42) %, which was lower than that in the control group (all P &lt; 0.05). For the subgroup comparison, as the NYHA class augmented, patients also had a significant increase in the mortality rate and the difference among subgroups had statistical significance (P &lt; 0.05). Furthermore, with 442 pg/mL as a critical point for BNP, patients in the research group were further divided into the BNP&gt;442 pg/mL group and BNP ≤442pg/mL group, and the statistical analysis revealed that in the BNP&gt;442 pg/mL group, the incidence rate of cardiovascular events, re-hospitalization rate and mortality rate were 53.53%, 14.14% and 7.07%, which were all significantly higher than those in the BNP ≤ 442 pg/mL group (all P &lt; 0.05). Also, BMP gene expression was increased in NYHA II, NYHA III, and NYHA IV groups compared to the control group. However, this increase was statistically significant in the NYHA III group (P &lt;0.05) and in the NYHA IV group (P &lt;0.01) compared to the control group. In conclusion, the level of BNP in plasma can reflect the condition of CHF and is critical to the clinical diagnosis, treatment and prognosis evaluation and evaluation of the BNP gene confirmed the result. Thus, it is worth being promoted in clinical practice.

Abstract 9555: A Mean Hemoglobin A1c Level of 7,5% is a Cliff Value for the Development of Cardiovascular Events in Diabetic Patients

Background: We sought to evaluate whether there was a difference in the incidence rate of cardiovascular event (CVD) among different hemoglobin (Hb) A1c levels in diabetic patients without a history of atherosclerotic events. Methods: The Japanese primary prevention of atherosclerosis with aspirin for diabetes (JPAD) trial was a multicenter, prospective, randomized, open label, blinded, end-point study done from 2002 to 2008. After completion of the JPAD trial, we followed up with the patients until 2019. We defined the cardiovascular events as the following: acute myocardial infarction; stable angina; unstable angina; sudden cardiac death; stroke; transient ischemic attack; aortic disease; and peripheral artery disease. Among 2,535 JPAD patients, HbA1c levels of the JPAD patients were recorded on average 8 times. Based on the mean value of HbA1c, we divided the patients into three groups: a High HbA1c Group (n=899, HbA1c ≥7.5%); a Moderate HbA1c Group (n=581, 7.5% &gt;HbA1c ≥7.0 %); or, a Low HbA1c Group (n=1055, 7.0% &gt;HbA1c). We compared the incidence of CVD among the three groups. Results: The mean HbA1c (%) was 8.6 in the High HbA1c Group, 7.4 in the Moderate HbA1c Group, and 6.6 in the Low HbA1c Group on registration. During an 11.56-year follow-up, the incidence of CVD was significantly higher in the High HbA1c Group (P&lt;0.0001, Figure) but was not significantly different between the Moderate HbA1c and the Low HbA1c Groups. Cox proportional hazards model analysis revealed that a High HbA1c level (HR, 1.61: 1.26-2.05, P=0.0001) was an independent factor after adjustment for proteinuria ≥±, age ≥65 years, male, body mass index ≥24 kg/m 2 , duration of diabetes ≥7.0% years, medications, eGFR ≥60 ml/min/1.73m 2 , and systolic blood pressure ≥140 mm Hg (Figure). Conclusions: Our study demonstrated that HbA1c ≥7.5% was independently associated with the incidence of CVD in diabetic patients without a history of atherosclerotic events while 7.5% &gt;HbA1c ≥7.0 % was not.

The relationship between diastolic blood pressure and the risk of cardiovascular events in patients with atrial fibrillation whose systolic blood pressure was treated to less than 130 mmHg

Abstract Background Hypertension is one of the major risk factors of cardiovascular events in patients with atrial fibrillation (AF). Low diastolic blood pressure (DBP) has been reported to be associated with the incidence of cardiovascular events, but current guidelines recommend an intensive blood pressure target of less than 130/80 mmHg for AF patients taking oral anticoagulants without mentioning the lower limits of DBP. Methods The Fushimi AF Registry is a community-based prospective survey of AF patients in a city of Japan. Follow-up data were available in 4,472 patients, and hypertensive patients who received prescription of any antihypertensive agents and whose systolic blood pressure was treated to less than 130 mmHg were available were examined (n=1,319). We divided the patients into four groups according to their DBP at baseline; G1 (DBP&amp;lt;60 mmHg, n=349), G2 (60≤DBP&amp;lt;70, n=434), G3 (70≤DBP&amp;lt;80, n=386) and G4 (80≤DBP, n=150), and compared the clinical background and outcomes among groups. Results The proportion of female was grater in G1 group, and the patients in G1 group were older. During the median follow-up of 2,458 days, in Kaplan-Meier analysis, the incidence rates of cardiovascular events (composite of cardiac death, ischemic stroke, systemic embolism, non-fatal myocardial infarction and heart failure hospitalization during follow up) were the highest in G1 group and the lowest in G3 group (G1: 7.2% per person-year vs. G2: 4.9% vs. G3: 2.2% vs. G4: 4.4%; p&amp;lt;0.01). Multivariate Cox proportional hazards regression analysis revealed that DBP was an independent determinant of cardiovascular events (G1 vs. G3; hazard ratio (HR): 1.96, 95% confidence intervals (CI): 1.39–2.76, G2 vs. G3; HR: 1.79, 95% CI: 1.28–2.50, G4 vs. G3; HR: 1.56, 95% CI: 0.99–2.45) (Figure 1). When we examined the association of DBP according to 10 mmHg increment, patients with excessively low DBP (&amp;lt;50 mmHg) had significantly higher incidence of cardiovascular events than patients with DBP of 70–79 mmHg (HR: 2.80, 95% CI: 1.81–4.33), and DBP exhibited J curve association with higher incidence of cardiovascular events (Figure 2). Conclusion In Japanese AF patients whose systolic blood pressure was treated to less than 130 mmHg, patients with excessively low DBP had significantly higher incidence of cardiovascular events, and DBP exhibited J curve association with higher incidence of cardiovascular events. Funding Acknowledgement Type of funding sources: None.

The potential role of EHR data in optimizing eligibility criteria definition for cardiovascular outcome trials

BackgroundCardiovascular outcome trials (CVOTs) include patients with high risks for cardiovascular events based on specific inclusion criteria. Little is known about the impact of such inclusion criteria on patient accrual and the incidence rate of cardiovascular events. Materials and methodsWe evaluated the impact of criteria on the accrual and the number of cardiovascular events in a cohort of 1544 diabetes patients identified from the clinical data warehouse of New York Presbyterian Hospital / Columbia University Irving Medical Center. ResultsThe highest incidence rate of the composite events (i.e., cardiovascular mortality, stroke, and myocardial infarction) was observed when the inclusion criteria seek patients with underlying cardiovascular diseases or age ≥ 60 with at least two of the risk factors including duration of diabetes, hypertension, dyslipidemia, smoking status, and albuminuria. ConclusionOur study shows that the electronic health records could be utilized to optimize the inclusion criteria while balancing study inclusiveness and number of events.

MO540CARDIOVASCULAR OUTCOMES ASSOCIATED WITH ACHIEVED HAEMOGLOBIN LEVEL IN POOLED PHASE 3 STUDIES OF ROXADUSTAT IN NON-DIALYSIS-DEPENDENT PATIENTS WITH ANAEMIA

Abstract Background and Aims Randomised clinical trials evaluating anaemia correction using erythropoietin-stimulating agents (ESAs) in chronic kidney disease (CKD) patients have demonstrated an association between ESA use and increased risk of cardiovascular (CV) complications and mortality. Although the mechanism for this increased risk remains unclear, possibilities include rapid rates of rise (ROR) in haemoglobin (Hb), exposure to high ESA dose and dose escalation, a high Hb target range, and off-target effects of ESAs. Thus, current recommendations generally state that Hb levels should be maintained between 10 and 12 g/dL. Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), is used for the treatment of anaemia of CKD; roxadustat stimulates endogenous production of erythropoietin and enhances iron availability, thereby supporting red blood cell production. In this pooled analysis, we explored the relationship between 1) achieved Hb levels and 2) preliminary data for ROR of Hb and subsequent incidence rates of CV events in non–dialysis-dependent (NDD) CKD patients who received roxadustat. Method We analysed pooled data from four phase 3 studies in NDD patients (placebo-controlled: ALPS, ANDES, OLYMPUS; ESA-controlled: DOLOMITES) with anaemia of CKD who received any dose of roxadustat. The reported events occurred during the treatment period and within 7 days of the last dose of roxadustat. Incidence rates of adjudicated major adverse CV events (MACE: all-cause mortality [ACM], myocardial infarction, and stroke), MACE+ (MACE plus heart failure and unstable angina requiring hospitalisation), and ACM were examined relative to 1) most recent Hb level before the event and 2) the preliminary data for ROR of Hb within the 4 weeks of treatment immediately prior to the event. Results Overall, 2709 patients were randomised and received roxadustat. Incidence rates of MACE, MACE+, and ACM were 3- or 4-fold higher in patients with lower reported Hb levels (Hb &amp;lt;10 g/L) compared with those who achieved Hb ≥10 g/dL. Incidence rates of MACE, MACE+, and ACM were similar or lower in patients with a maximum rise of &amp;gt;2 g/dL in Hb within the 4-week period prior to the event compared to those with a change of ≤2 g/dL within the same period (Table). However, it should be noted that patient-exposure years (PEY) were low for the subgroup of patients with ROR &amp;gt;2 g/dL (∼3.3% of overall PEY), and patients with a decreasing Hb were included in the ≤2 g/dL/4 weeks subgroup. Conclusion In this analysis of roxadustat-treated patients with NDD CKD, incidence rates of MACE, MACE+, and ACM were lower in patients who achieved target Hb levels of 10-12 g/dL compared with patients who achieved Hb &amp;lt;10 g/dL. Risk of MACE, MACE+, or ACM did not appear to be associated with the proximal preliminary data for ROR of Hb; however, further characterisation of the ROR of Hb and ROR in relation to baseline Hb are warranted.

POS0213 20 Year Follow-Up Of Cardiovascular Event Risk In Rheumatoid Arthritis Compared To Diabetes

Background:Patients with rheumatoid arthritis have an increased risk for developing cardiovascular diseases (CVD) compared to the general population, similar to the CVD risk in patients with diabetes mellitus. However, there are no controlled studies investigating the incidence of cardiovascular (CV) events in RA patients with follow up of more than 20 years.Objectives:The objectives of the current study were to investigate the incidence rates of CV events in a long-term follow up cohort of RA patients, and to compare these to a similar cohort representing the general population, ie. The Hoorn study.Methods:The CARRÉ study is an ongoing prospective cohort study, which started in 2001, investigating CV mortality and morbidity in 353 randomly selected patients with RA. Primary endpoints, i.e. verified medical history of coronary, cerebral or peripheral arterial disease, were determined at baseline, and after three, ten, fifteen and twenty years of follow up. Patients were censored at the date of an experienced CV event or their death. Incidence density rates per 100 patient years were calculated. Data were compared to results from the Hoorn study, a Dutch cohort study of glucose metabolism and other CV risk factors that began in 1989. All 2,484 participants were subject to an extensive and repeated CV screening program similar to that used in the CARRÉ study.Results:After 20 years of follow up 118 patients (33%) developed at least one CV event in the Carré group. Mean (SD) follow up time was 11 (6) years with a total of 3,500 years at risk and an incidence rate of 3.4 per 100 patient-years; this is slightly up from the figure reported at 15 years, i.e. 3.2 per 100 patient-years. A CV event-free survival curve is shown in figure 1. After 30 years of follow up, 295 participants of the Hoorn study had developed a CV event, during a mean follow up time 20 (8) years. Total time at risk was 50,000 years, with an incidence rate of 0.6 CV events per 100 patient years.Conclusion:In our cohort the incidence rate of CV events in RA patients has remained consistently high when compared with the general population, despite better control of RA inflammation in recent years. This again confirms the need for timely CVD-risk screening and management.

THE DEVELOPMENT OF RESISTANT HYPERTENSION INDEPENDENT OF THE PRECEDING PERIOD OF THE BLOOD PRESSURE CONTROL IS ASSOCIATED WITH THE INCREASED RISK OF CARDIOVASCULAR EVENTS AND DEATH

Objective: Resistant hypertension (RH) is associated with the increased risk of cardiovascular events (CVEs); that excess risk is often attributed to the legacy of the previous period of uncontrolled blood pressures (BPs). We used the database of the ASCOT trial to evaluate the risk of CVEs (non-fatal myocardial infarction, fatal coronary heart disease, and fatal/non-fatal stroke) and death, after controlling for the cumulative mean of BPs for a preceding period of 2-years (using area-under-curve [AUC]). Design and method: 18,926 hypertensive patients were initially followed up for the development of RH or not for a period of 2-years. During that period, we calculated the AUC of the cumulative mean BPs (AUCcmBPs) until the RH diagnosis or the end of the 2-year period if no-RH. These patients were then followed up from this new baseline for the risk of CVEs or death. We estimated incidence rates and developed a multivariable Cox regression model after adjusting for a-priori confounders (age, sex, socio-economic status, BMI, total cholesterol, HDL-cholesterol, systolic-BP at baseline, randomized treatment allocation, diabetes, other vascular diseases) and the AUCcmBPs. Interaction tests were done for those who were taking antihypertensive medications prior to the randomization or not. Results: About one-third (n = 5,660) developed RH by the end of 2-years. During the further median follow-up of 3.9 years, there were 1113 CVEs and 745 deaths. The incidence rate of CVE and death was higher in those with RH vs those without (34.8 and 18.9 per 1,000 person-years vs 24.0 and 15.4, respectively). In the multivariable model after controlling for the AUCcmBPs, those with RH, as compared to those without, had a significantly higher risk of CVE and death (HR: 1.15 [95% CI 1.03–1.27], p-value = 0.010, and 1.16 [1.02–1.33], p-value = 0.028, respectively). This excess in the risk didn’t differ significantly between those who were on prior antihypertensive therapy or not (interaction test p-value = 0.430 and p-value = 0.310, respectively). Conclusions: After accounting for prior BPs, the presence of RH is associated with the increased risk of CVEs and death; which could be because of the additional risk due to associated genotypical or phenotypical factors.

Certain beta blockers (e.g., bisoprolol) may be reevaluated in hypertension guidelines for patients with left ventricular hypertrophy to diminish the ventricular arrhythmic risk

Hypertensive left ventricular hypertrophy (HTN LVH) is associated with almost threefold increased risk of ventricular tachycardia (VT)/ventricular fibrillation (VF). Furthermore, HTN LVH increases the risk of sudden cardiac death (SCD). The reverse LV remodeling due to efficient antihypertensive therapy lowers the incidence rates of cardiovascular events and SCD and the vast majority of available arterial hypertension (HTN) guidelines recommend renin angiotensin system (RAS) blockers and calcium channel blockers (CCBs) for HTN LVH aiming for LVH regression. On the other hand, beta blockers (BBs) as a class are not recommended in HTN LVH due to their insufficient capacity to reverse LVH remodeling even though they are recommended as the first-line drugs for prevention/treatment of VT/VF (in general, unrelated to HTN LVH). Moreover, BBs are the best antiarrhythmic (against VT/VF) among antihypertensive drugs. Despite that, BBs are currently not recommended for LVH treatment in HTN Guidelines. It is important to prevent VT/VF in patients at high risk, such as those with HTN LVH. Therefore, certain BBs (such as Bisoprolol) may be reevaluated in guidelines for HTN (in the section of HTN LVH).

Cardiovascular risk in patients with spondyloarthritis and association with anti-TNF drugs.

Background:Cardiovascular (CVS) diseases are the leading cause of death worldwide and patients with rheumatic diseases have an increased CVS. CVS risk factors and CVS events are common in spondyloarthritis (SpA). Delineating the CVS risk in patients with SpA and identifying modifiable risk factors would be useful.Methods:Patients with SpA and patients with non-specific back pain (NSBP) were identified in rheumatology and orthopedics clinics, respectively. Clinical information and CVS events were retrieved. Baseline characteristics and incidence rates of CVS events were compared between two groups of patients using an age- and sex-matched cohort. Propensity score adjustment and Cox regression analysis were performed to determine the CVS risk associated with SpA.Results:A total of 5046 patients (SpA 2616 and NSBP 2430) were included from eight centers. Over 56,484 person-years of follow up, 160 strokes, 84 myocardial infarction (MI) and 262 major adverse cardiovascular events (MACE) were identified. Hypercholesterolemia was more prevalent in SpA (SpA 34.2%, NSBP 28.7%, p < 0.01). Crude incidence rates of MACE and stroke were higher in SpA patients. SpA was associated with a higher risk of MACE [hazard ratio (HR) 1.70; 95% confidence interval (CI) 1.29–2.26; p < 0.01] and cerebrovascular events (HR 1.50; 95% CI 1.08–2.07; p = 0.02). SpA patients with anti-TNF use had a reduced risk of MACE (HR 0.37, 95%CI 0.17–0.80, p = 0.01) and cerebrovascular events (HR 0.21, 95%CI 0.06–0.78, p = 0.02) compared with SpA patients without anti-TNF use.Conclusion:SpA is an independent CVS risk factor. Anti-tumor necrosis factor (TNF) drugs were associated with a reduced CVS risk in these patients.