Cumulative Incidence Of Cardiovascular Events Research Articles

Factors associated with treatment responses to pioglitazone in patients with steatotic liver disease: A 3-year prospective cohort study.

The response rate to pioglitazone and the predictive factors for its effects on improving liver biochemistry in patients with steatotic liver disease (SLD) remain elusive, so we aimed to investigate these issues. A 3-year prospective cohort study of 126 Taiwanese patients with SLD treated with pioglitazone (15-30 mg/day) was conducted. Phospholipase domain-containing protein 3 I148M rs738409, methylenetetrahydrofolate reductase rs1801133, aldehyde dehydrogenase 2 (ALDH2) rs671 and lipoprotein lipase rs10099160 single nucleotide polymorphisms were assessed in the patients. Of 126 patients, 78 (61.9%) were men, and the mean and median ages were 54.3 and 56.5 years, respectively. Pioglitazone responders were defined as those with decreased alanine aminotransferase (ALT) levels at 6 months post-treatment, and 105 (83.3%) patients were responders. Compared with non-responders, responders were more frequently women and had higher baseline ALT levels. The proportion of patients with the ALDH2 rs671 GG genotype was lower among responders (38.6% vs. 66.6%, p = .028). Female sex [odds ratio (OR): 4.514, p = .023] and baseline ALT level (OR: 1.015, p = .046; cut-off level: ≥82 U/L) were associated with pioglitazone response. Among responders, the liver biochemistry and homeostasis model assessment of insulin resistance improved from 6 to 24 months post-treatment. The total cholesterol levels decreased within 6 months, while increases in high-density lipoprotein cholesterol levels and decreases in triglyceride levels and fibrosis-4 scores were noted only at 24 months post-treatment. The 2-year cumulative incidences of cardiovascular events, cancers and hepatic events were similar between responders and non-responders. Regarding liver biochemistry, over 80% of Taiwanese patients with SLD had a pioglitazone response, which was positively associated with female sex and baseline ALT levels. Insulin resistance improved as early as 6 months post-treatment, while liver fibrosis improvement was not observed until 24 months post-treatment. The link between the pioglitazone response and the ALDH2 genotype warrants further investigation.

Intermediate and long-term residual cardiovascular risk in patients with established cardiovascular disease treated with statins.

Statins remain the first-line treatment for secondary prevention of cardiovascular (CV) events, with lowering of low-density lipoprotein cholesterol (LDL-C) being their therapeutic target. Although LDL-C reduction significantly lowers CV risk, residual risk persists, even in patients with well-controlled LDL-C; thus, statin add-on agents that target pathways other than LDL-C, such as the omega-3 fatty acid eicosapentaenoic acid, may help to further reduce persistent CV risk in patients with established CV disease. This narrative review examines the contemporary literature assessing intermediate- and long-term event rates in patients with established CV disease treated with statins. CV event rates among patients treated with statins who have established CV disease, including coronary artery disease, cerebrovascular disease, or peripheral arterial disease, accumulate over time, with a cumulative incidence of CV events reaching up to approximately 40% over 10 years. Recurrent stroke occurs in up to 19% of patients seven years after a first cerebrovascular event. Repeat revascularization and CV-related death occurs in up to 38% and 33% of patients with peripheral artery disease after three years, respectively. Additional treatment strategies, such as eicosapentaenoic acid, are needed to reduce persistent CV risk in patients with established CV disease treated with statins.

Cardiovascular adverse events in patients with hepatocellular carcinoma receiving vascular endothelial growth factor inhibitors.

Vascular endothelial growth factor inhibitors, including tyrosine kinase inhibitors (TKIs) and anti-angiogenics, are first-line therapies for advanced and metastatic hepatocellular carcinoma. Although TKIs have a greater potential for off-target adverse effects compared with bevacizumab (anti-angiogenics), a direct comparison of the risk of cardiovascular adverse events between these two types of therapies has not been performed. To compare the incidence of and characterize cardiovascular adverse events in patients with hepatocellular carcinoma receiving TKIs versus bevacizumab. This cohort study included adult patients with hepatocellular carcinoma who received first-line TKIs (sorafenib or lenvatinib) or bevacizumab at two academic medical centers and one community cancer center from September 2018 to August 2021. The primary outcome was risk of cardiovascular adverse events. Major secondary outcomes included the incidence of individual types of cardiovascular adverse events and risk factors associated with major adverse cardiovascular events (MACE). The study included 221 patients (159 TKI patients; 62 bevacizumab patients). At a median follow-up of 5 months, the probability of cardiovascular adverse events was not significantly different between the two groups (hazard ratio [HR]: 0.85; 95% confidence interval [95% CI]: 0.58-1.24; p = 0.390). The cumulative incidence of cardiovascular events was highest in patients receiving lenvatinib (sub-distribution hazard ratio [SHR]: 1.53; 95% CI: 1.02-2.30) compared with those receiving sorafenib (reference) or bevacizumab (SHR: 1.05; 95% CI: 0.68-1.64) after adjustment for comorbidities, liver transplant status, and presence of portal vein thrombosis at baseline. Cardiovascular adverse events were observed in 151 (68%) patients, and MACE were observed in 27 (12%) patients. Risk factors associated with MACE were hypertension (SHR: 3.5; 95% CI: 0.9087-15.83; p = 0.086), prior history of MACE (SHR: 2.01; 95% CI: 0.83-4.87; p = 0.124), and tobacco use (SHR: 2.85; 95% CI: 0.90-8.97; p = 0.074). Cardiovascular risk was not significantly different between TKIs and bevacizumab. Lenvatinib appears to have the highest risk of cardiovascular adverse events among these first-line VEGF inhibitors.

A deep-learning-based retinal cardiovascular disease biomarker and risk of stroke, myocardial infarction, atrial fibrillation, and heart failure in the UK Biobank

Abstract Background Retinal photographs allow a non-invasive way to see the human vasculature and provide insights into cardiovascular disease (CVD). In our previous study, we developed the Reti-CVD, a deep-learning algorithm to predict the future CVD events from retinal photographs. Purpose In this study, we extend the application of Reti-CVD by investigating the association between the Reti-CVD score and the occurrence of individual cardiovascular events, including stroke, myocardial infarction (MI), atrial fibrillation (AF), and heart failure (HF). Methods The Reti-CVD scores were calculated and stratified into three risk groups based on optimized cut-off values from the UK Biobank. The cumulative incidence of cardiovascular events (stroke, MI, AF, and all-cause HF each) rate was evaluated across the three groups (low, moderate, and high risk) defined by the Reti-CVD score. Cox proportional hazards model was used to estimate the adjusted hazard ratios (aHRs), trends in HRs, and respective p-values were examined by fitting a linear model for the three categories after adjustment of age, gender, diabetes, hypertension, hyperlipidemia, and smoking. C-statistics was used to assess the prognostic value of the Reti-CVD score. Results A total of 44,677 participants were included at baseline and tracked for up to 7 years. There were 277 (0.62%) strokes, 506 (1.13%) MIs, 1053 (2.32%) AFs, and 431 (0.94%) HFs. An increase in Reti-CVD score was significantly associated with increased risk of stroke (adjusted hazard ratio [aHR] trends, 1.40; 95% confidence interval [CI], 1.09-1.80, p=0.008), MI (aHR trends, 1.22; 95% CI, 1.01-1.08, p<0.001), and AF (aHR trends, 1.33; 95% CI, 1.17-1.52, p<0.001). However, the association of Reti-CVD score-based three-risk groups and the occurrence of HF showed a trend for increased risk without statistical significance (aHR trends, 1.17; 95% CI, 0.96-1.43, p=0.123). C statistics based on Reti-CVD alone were 0.65 (0.63-0.68) for stroke, 0.64 (0.62-0.66) for MI, 0.66 (0.65-0.67) for AF, and 0.65 (0.60-0.70) for HF. Conclusion A deep-learning-based retinal CVD biomarker, the Reti-CVD has the potential to identify individuals with a risk of stroke, MI, and AF, who are likely to benefit from earlier preventative CVD interventions. For the relationship between the Reti-CVD and HF, it seems necessary to analyze by HF subtypes.

Cognitive decline assessed using a brief screening test and cardiovascular and non-cardiovascular events in older patients with heart failure.

Although cognitive decline is recognized as a prognostic factor of heart failure (HF), the association of cognitive decline with specific clinical outcomes in patients with HF remains unclear. This study examines the relationship between cognitive decline using a brief test and cardiovascular and non-cardiovascular events in older patients with HF. This study included 146 hospitalised patients with HF (median age, 77years; male, 56.8%). Cognitive decline was defined as a score of ≤ 9 points on the Rapid Dementia Screening Test at the time of discharge. Cumulative incidence of cardiovascular events after discharge was twofold higher in patients with cognitive decline (Model 1 adjusted for basic characteristics, hazard ratio (HR) = 2.01, 95% confidence interval (CI): 0.94-4.31; Model 2 adjusted for potential confounders, HR = 2.30, 95% CI: 1.07-4.97). The association between cognitive decline and non-cardiovascular events decreased after adjusting for potential confounders. The results of this study emphasize the clinical utility of cognitive assessment for risk stratification of worsening cardiovascular conditions, including HF.

Cardiovascular Events After Hematopoietic Stem Cell Transplant: Incidence and Risk Factors

BackgroundHematopoietic stem cell transplantation (HSCT) is associated with various cardiovascular (CV) complications. ObjectivesWe sought to characterize the incidence and risk factors for short-term and long-term CV events in a contemporary cohort of adult HSCT recipients. MethodsWe conducted a multicenter observational study of adult patients who underwent autologous or allogeneic HSCT between 2008 and 2019. Data on demographics, clinical characteristics, conditioning regimen, and CV outcomes were collected through chart review. CV outcomes were a composite of CV death, myocardial infarction, heart failure, atrial fibrillation/flutter, stroke, and sustained ventricular tachycardia and were classified as short-term (≤100 days post-HSCT) or long-term (>100 days post-HSCT). ResultsIn 3,354 patients (mean age 55 years; 40.9% female; 30.1% Black) followed for a median time of 2.3 years (Q1-Q3: 1.0-5.4 years), the 100-day and 5-year cumulative incidences of CV events were 4.1% and 13.9%, respectively. Atrial fibrillation/flutter was the most common short- and long-term CV event, with a 100-day incidence of 2.6% and a 5-year incidence of 6.8% followed by heart failure (1.1% at 100 days and 5.4% at 5 years). Allogeneic recipients had a higher incidence of long-term CV events compared to autologous recipients (5-year incidence 16.4% vs 12.1%; P = 0.002). Baseline CV comorbidities were associated with a higher risk of long-term CV events. ConclusionsThe incidence of short-term CV events in HSCT recipients is relatively low. Long-term events were more common among allogeneic recipients and those with pre-existing CV comorbidities.

Impact of Cardiovascular Comorbidities on the Effectiveness and Safety of Bevacizumab in Older Patients with Metastatic Colorectal Cancer.

Cardiovascular comorbidities are not contraindications of bevacizumab for metastatic colorectal cancer. We aimed to evaluate the impact of cardiovascular comorbidities before bevacizumab treatment on overall survival and cardiovascular safety in older patients with metastatic colorectal cancer. A 2009-2015 cohort of patients with metastatic colorectal cancer aged ≥65 years administered first-line bevacizumab was extracted from the French healthcare reimbursement claims database. Baseline heart failure, hypertension, and venous/arterial thromboembolic events were identified. The 36-month overall survival rate was evaluated using the Kaplan-Meier method, and the impact of cardiovascular comorbidities on the 36-month overall survival using a time-dependent, multivariable, Cox proportional hazards model. The 36-month cumulative incidence of cardiovascular events, and the impact of cardiovascular comorbidities on the likelihood of cardiovascular events were evaluated using the Fine and Gray model, with death as a competing risk. We included 9222 patients (56.4% male; median age 73 years). Two-thirds (66.7%) had baseline cardiovascular comorbidities. The median 36-month overall survival was 20.4 [95% confidence interval (CI) 19.9-21.0] and 21.8 [95% CI 21.1-22.6] months in patients with and without cardiovascular comorbidities, respectively. Age ≥75 years, dependency in activities of daily living, radiotherapy, and another targeted therapy were identified as death risk factors, but not cardiovascular comorbidities. At 36 months, cardiovascular events had occurred in 60.2% [95% CI 58.9-61.4] and 44.1% [95% CI 42.3-45.9] of patients with and without cardiovascular comorbidities. Baseline venous thrombosis, female, three or more cardiovascular medications, another targeted therapy, and more than six bevacizumab injections were identified as risk factors for cardiovascular events. In clinical practice, cardiovascular comorbidities before administering bevacizumab to older patients with metastatic colorectal cancer impacted the cardiovascular safety, but not overall survival. Unless they limit functional independency, older patients with cardiovascular comorbidities should be treated with bevacizumab under close monitoring.

Impact of fibrosis on liver-related event incidence in nonalcoholic fatty liver disease: A multicenter observational study.

There are few reports on the prognosis of liver-related events in Japanese patients with nonalcoholic fatty liver disease (NAFLD). We undertook an observational study to compare the prognosis between fibrotic and nonfibrotic groups in Japanese NAFLD patients. Prognosis in 393 NAFLD patients who underwent liver biopsy between April 2013 and April 2015 at multiple centers were investigated. The time to onset of liver-related events, cardiovascular events, development of extrahepatic cancers, and death were compared between the pathologically fibrotic nonalcoholic steatohepatitis (NASH) group and nonalcoholic fatty liver (NAFL)+nonfibrotic NASH group. A similar analysis was carried out based on the fibrotic classification diagnosed using four noninvasive fibrosis prediction models. The mean age and body mass index at the time of liver biopsy was 55.7years old and 28.04kg/m2 , respectively The cumulative incidence of liver-related events at 1080days after liver biopsy was 5.79% in the pathologically fibrotic NASH group and 0% in the NAFL+nonfibrotic NASH group, with a significant difference (p=0.0334). The cumulative incidence of liver-related events was significantly higher in the positive group for the prediction model than in the negative group in all four models (all p values were <0.0001). There was no significant difference between the pathologically fibrotic NASH group and NAFL+nonfibrotic NASH group in terms of cumulative incidence of cardiovascular events, development of extrahepatic cancers, and death. The incidence of liver-related events was significantly higher in the fibrotic NASH group than that of the NAFL+nonfibrotic NASH group in Japanese NAFLD patients.

Long-term clinical outcomes of adults with metabolic dysfunction-associated fatty liver disease: a single-centre prospective cohort study with baseline liver biopsy.

There are limited data on the long-term adverse clinical outcomes of adults with metabolic dysfunction-associated fatty liver disease (MAFLD). This is a single-centre prospective study of a well-characterized cohort of MAFLD patients who underwent liver biopsy and followed every 6-12months for adverse clinical outcomes. The data for 202 patients were analyzed [median age 55.0 (48.0-61.3) years old; male, 47.5%; obese, 88.6%; diabetes mellitus, 71.3%; steatohepatitis, 76.7%; advanced fibrosis, 27.2%]. The median follow-up interval was 7 (4-8) years. The cumulative incidence of liver-related events, cardiovascular events, malignancy and mortality was 0.43, 2.03, 0.60 and 0.60 per 100 person-years of follow-up, respectively. Liver-related events were only seen in patient with advanced fibrosis at 9.1% vs 0% in patient without advanced liver fibrosis (p < 0.001). The cumulative incidence of liver-related events among patients with advanced fibrosis was 1.67 per 100 person-years of follow-up. When further stratified to bridging fibrosis and cirrhosis, the cumulative incidence of liver-related events was 1.47 and 3.85 per 100 person-years of follow-up, respectively. Advanced fibrosis was not significantly associated with cardiovascular events, malignancy or mortality. The cumulative incidence of liver-related events, cardiovascular events, malignancy and mortality were not significantly different between patients with and without steatohepatitis and between obese and non-obese patients. However, liver-related events were only seen among obese patients. Overall, the cumulative incidence of liver-related event is low in patients with MAFLD, but it is much higher among those with advanced fibrosis. However, there is a relatively high cumulative incidence of cardiovascular event among patients with MAFLD.

Correlation between fluid parameter and cardiovascular events in hemodialysis patients based on repeated body composition analyses

Objective: To explore the correlation between fluid load index and cardiovascular events in hemodialysis patients based on repeated body composition analyses. Methods: A prospective cohort study was conducted to collect the clinical data of patients undergoing maintenance hemodialysis (MHD) in the Department of Nephrology, Hangzhou Hospital of Traditional Chinese Medicine from July to September 2020. The pre-dialysis fluid overload (FO) index-overhydration (OH) was measured by bioelectrical impedance method, and the follow-up monitoring was conducted every 6 months. According to the baseline OH value, patients were divided into non-FO group (OH≤2.5 L) and FO group (OH>2.5 L). Moreover, according to the repeated measurements, the patients were divided into continuous non-FO group, continuous FO group and intermittent FO group. All patients were followed up until October 1, 2022, and the outcomes were recorded. The end point of follow-up was cardiovascular events. The cumulative incidence of cardiovascular events was calculated by the Kaplan-Meier method, and the risk factors of cardiovascular events were analyzed by Cox proportional hazards regression model. Results: A total of 289 patients were included, including 88 patients (30.4%) with FO and 201 patients (69.6%) with non-FO. There were 168 males (58.1%) and 121 (41.9%) females, with an average age of (58±13) years and an average follow-up time of (22.0±6.5) months. Kaplan-Meier analysis showed that the incidence of cardiovascular events in the baseline FO group was higher than that in the non-FO group (log-rank χ2=14.44, P<0.001). The incidence of cardiovascular events in both the continuous FO group and the intermittent FO group was higher than that in the continuous non-FO group (log-rank χ2=41.47, P<0.001; log-rank χ2=18.36, P<0.001). After adjustment for gender, age, comorbidities, and biochemical indicators, the incidence of cardiovascular events in the baseline FO group was 1.850 times of the non-FO group (95%CI: 1.046-3.271, P=0.034). The incidence of cardiovascular events in the continuous FO group was 4.679 times of the continuous non-FO group (95%CI: 2.189-10.002, P<0.001). The incidence of cardiovascular events in the intermittent FO group was 3.410 times of the continuous non-FO group (95%CI: 1.696-6.857, P=0.001). Conclusions: OH value measured by bioelectrical impedance can be used as an important reference index for clinical monitoring of cardiovascular events in MHD patients. Continuous chronic and intermittent exposures to FO are risk factors for cardiovascular events in hemodialysis patients.

Association between salt intake and long-term mortality in hemodialysis patients: A retrospective cohort study.

BackgroundThe association between salt intake and clinical outcomes in hemodialysis patients has been controversial. This study aimed to clarify the association between salt intake and mortality in hemodialysis patients.MethodThe present study included patients who underwent hemodialysis from June 1st 2016 to May 31st 2020. Corrected salt intake by ideal body weight was the main predictor of outcomes. Ideal body weight was calculated assuming that the ideal body mass index is 22 kg/m2 for the Japanese population. The multivariate Cox proportional hazards model was used to determine the association between corrected salt intake and mortality, adjusting for potential confounders. The outcomes considered were all-cause mortality and cumulative incidence of cardiovascular events at year 4.ResultA total of 492 adult patients were enrolled in the study. The mean daily salt intake and corrected salt intake at baseline were 9.5 g/day and 0.17 g/kg/day, respectively. The low corrected salt intake group (< 0.13 g/kg/day) demonstrated the highest 4-year all-cause mortality. No association was observed between corrected salt intake and the cumulative incidence of cardiovascular events. In multivariate Cox proportional hazards analysis, only the group with corrected salt intake of 0.16–0.20 g/kg/day was associated with a decreased hazard risk for all-cause death compared with the low corrected salt intake group.ConclusionThe present study found that a low salt intake was associated with high all-cause mortality in hemodialysis patients. Reduced long-term survival may be attributed to malnutrition resulting from excessive salt restriction.

Cardiovascular disease prediction model for Indonesian adult population with prediabetes and diabetes mellitus: The Bogor Cohort study of Noncommunicable Diseases Risk Factors

Background and aimsThis study aims to develop a predictive model of cardiovascular events in dysglycemia among the Indonesian adult population. MethodsThis is a retrospective cohort study conducted on subjects over 25 years in the “The Bogor Cohort Study of Noncommunicable Diseases Risk Factors” from 2011 to 2018. Data associated with age, gender, blood pressure, body mass index, waist circumference, blood glucose, cholesterol, smoking habits, family history of cardiovascular disease, and physical activity were obtained. Cardiovascular events in six years were observed; this included coronary heart disease, stroke, or all-cause cardiovascular mortality. Cox proportional hazards regression models were used to determine independent predictors of cardiovascular events. ResultsA total of 1085 subjects with prediabetes and diabetes mellitus were included in this study, with 73.5% female. The cumulative incidence of cardiovascular events in six years was 9.7%. Predictors of cardiovascular events were age ≥45 years (HR = 2.737; 95% CI 1.565–4.787) and hypertension (HR = 2.580; 95% CI 1.619–4.112). ConclusionsAge ≥45 years and hypertension were predictors of cardiovascular events in six years among the adult Indonesian population with prediabetes and diabetes, necessitating targeted intervention among these subjects.

Rates of cardiovascular events are significantly different across cancer types

Abstract Background As a result of the effects of both cancer treatment and underlying cardiovascular (CV) risk factors, patients with cancer have a 2 to 6-fold higher CV mortality rate than the general population. Certain cancer types appear to be associated with a greater CV risk, although much of our current understanding is limited to breast and pediatric cancer survivors. We sought to characterize the CV risk factor burden and incidence of CV events across different cancer types. Methods We included all patients diagnosed with 9 different cancer types (breast, lung, prostate, melanoma, myeloma, kidney, colorectal cancer, leukemia, or lymphoma) after June 1, 2011 in a large US administrative claims database (PharMetrics). Patients had continuous enrollment in the database for ≥12 months prior to cancer diagnosis, and were followed until they had a specified CV event or were disenrolled. Incidence rates for CV events were calculated and Cox proportional hazard multivariable models were used for time-to-event analysis for each cancer type, accounting for baseline CV risk factors. Results Over 800,000 patients with cancer were identified across the 9 cancer types. The incidence of CV events was generally &amp;gt;5-fold higher in lung cancer than in breast cancer. The adjusted hazard ratio for the combined CV events of myocardial infarction, stroke, unstable angina, and heart failure was 2.7 (95% confidence interval 2.6–2.7) for lung cancer relative to breast cancer, with a cumulative incidence of 25% by 4 years. Multiple myeloma and leukemia had the next highest cumulative incidence of CV events, while breast cancer and melanoma had the lowest (Table 1 and Figure 1). Conclusion CV events were significantly increased in certain cancer types, especially lung, multiple myeloma and leukemia, even after accounting for baseline CV risk factors. Patients with lung cancer had a 25% cumulative incidence of combined CV events within 4 years. Understanding the wide variation of CV events in patients with cancer can help inform CV risk factor modification and strategies to minimize CV toxicity, with the aim of reducing the risk of future CV events and improving the morbidity and mortality of cancer survivors. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bristol Meyers Squibb

Cardiovascular events among recipients of hematopoietic stem cell transplantation

Abstract Background Allogeneic and autologous hematopoietic stem cell transplantation (HSCT) are potential curative treatments for several hematological malignancies (1). Survival after HSCT has improved over the last decade, but survivors remain at risk for health issues after transplantation. Cardiovascular complications after HSCT are increasingly recognized (2). Cardiovascular diseases may be an important cause of mortality and morbidity in patients after HSCT owing to the toxicities of the cancer therapies; however, the incidence of cardiovascular events (CVEs) in this population has not been completely characterized. The objective of this systematic review is to summarize the evidence on the incidence of CVEs in HSCT recipients. Methods Medline and Embase were searched from inception to December 2020 without language restriction. Two authors independently screened the titles and abstracts. Inclusion criteria were: cohort studies and phase 3 randomized controlled trials that reported CVEs (i.e., heart failure, arrythmias, acute coronary syndrome, and stroke) or cardiovascular death among adults who underwent HSCT for a hematological malignancy. All-cause mortality, relapse-related mortality, and non-relapse-related mortality (NRM) were also collected. Studies in which the follow up period was not started immediately after HSCT were excluded due to the risk of immortal bias. Results Of 8151 nonduplicate articles, 30 studies including 14019 individuals post autologous HSCT, and 22 studies including 31049 individuals post allogeneic HSCT met the inclusion criteria. The cumulative incidence of CVEs in the first 100 days post autologous HSCT was 9% and arrhythmia (i.e., atrial fibrillation) was the most common CVE. In recipients of allogeneic HSCT, the 100-day cumulative incidence of CVEs was 3%, and heart failure (HF) was the most common reported CVE. In recipients of autologous and allogeneic HSCT, cardiovascular death was responsible for 43% and 10% of NRM within 100 days, respectively (Table 1). The incidence of CVEs was 4.96 per 1000-person years (95% CI; 4.21–5.80) in long-term survivors (beyond 100-days) of autologous HSCT, and HF was the most common CVE in this population. In long-term survivors of allogeneic HSCT, the incidence of CVEs was 1.90 per 1000-person years (95% CI: 1.59–2.24). Cardiovascular death was the most frequently reported CVE in long-term survivors of allogeneic HSCT (Table 2). Conclusion CVEs remain a major cause of non relapse morbidity and mortality in recipients of HSCT, especially recipients of autologous HSCT within the first 100 days. Future studies are needed to identify the risk factors for CVEs that are specific to HSCT recipients. Funding Acknowledgement Type of funding sources: None.

Cardiovascular events in cancer patients with bone metastases-A Danish population-based cohort study of 23,113 patients.

IntroductionThe incidence of cardiovascular events among cancer patients with bone metastases is poorly understood. We examined rates of cardiovascular events among cancer patients with bone metastases and mortality following such events.MethodsUsing Danish health registries, we identified all Danish cancer patients diagnosed with bone metastases (1994–2013) and followed them from bone metastasis diagnosis. We computed incidence rates (IR) per 100 person‐years and cumulative incidence for first‐time inpatient hospitalization or outpatient clinic visit for cardiovascular events, defined as myocardial infarction, ischemic stroke, or venous thromboembolism (VTE). We also analyzed all‐cause mortality rates including cardiovascular events as time‐varying exposure with adjustment for age, sex, and Charlson Comorbidity Index score. All analyses were performed overall and stratified by cancer type (prostate, breast, lung, and other).ResultsWe included 23,113 cancer patients with bone metastases. The cumulative incidence of cardiovascular events was 1.3% at 30 days, 3.7% at 1 year, and 5.2% at 5 years of follow‐up. The highest IR was observed for VTE, followed by ischemic stroke and myocardial infarction, both overall and by cancer types. Lung cancer patients with bone metastases had the highest incidence of cardiovascular events followed by prostate and breast cancer. Occurrence of any cardiovascular event was a strong predictor of death (5 years following the event, the adjusted hazard ratio was 1.8 [95% confidence interval: 1.7–1.9]).ConclusionCancer patients with bone metastases had a substantial risk of developing cardiovascular events, and these events were associated with a subsequent increased mortality. Our findings underscore the importance of continuous optimized prevention of and care for cardiovascular disease among cancer patients with bone metastases.

Accelerated cardiovascular risk after viral clearance in hepatitis C patients with the NAMPT-rs61330082 TT genotype: An 8-year prospective cohort study

ABSTRACT Involvement of extracellular nicotinamide phosphoribosyltransferase (eNAMPT, i.e., visfatin or pre-B-cell colony-enhancing factor), a cancer metabokine, in chronically hepatitis C virus (HCV)-infected (CHC) patients with sustained virological responses (SVRs) remains elusive. This 8-year prospective cohort study evaluated eNAMPT profiles of 842 consecutive CHC patients, including 519 who had completed an anti-HCV therapy course and pre-therapy and 24-week post-therapy surveys. For 842 patients, pre-therapy associations were HCV RNA, homeostatic model assessment for insulin resistance (HOMA-IR) index, and body mass index with eNAMPT levels, and NAMPT-rs61330082 T allele with total cholesterol levels. NAMPT-rs10953502, NAMPT-rs2058539, and NAMPT-rs61330082 were in a linkage disequilibrium block, which was associated with total cholesterol levels. Compared to pre-therapy levels, at 24 weeks post-therapy, decreased eNAMPT and increased lipid levels were observed in SVR patients (n = 427). Among SVR patients, higher cumulative incidences of cardiovascular events occurred in those with a NAMPT-rs61330082 TT genotype than those with non-TT genotypes (28.2% vs. 8.4%, p < 0.001). NAMPT-rs61330082 TT genotype was independently associated with incident cardiovascular events (95% CI hazard ratio (HR): 1.88–10.37; HR: 4.415); no eNAMPT profiles were associated with incident malignancies. Of CHC patients, hepatic vascular endothelial cells and baseline peripheral leukocytes expressed higher eNAMPT levels than controls, and peripheral eNAMPT-positive leukocyte proportions decreased after SVR. During HCV infection, eNAMPT involvement in glucose metabolism was modulated by HCV RNA linked to lipid metabolism and NAMPT-associated SNPs. Hepatic endothelial cells and peripheral leukocytes potentially secrete eNAMPT. Caution is required for incident cardiovascular events in SVR patients with NAMPT-rs61330082 TT genotype.

Is the N-terminal pro-B-type natriuretic peptide a predictor of cardiovascular events in hemodialysis patients?

Aim To evaluate the role of N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) as a predictor of cardiovascular events (CVE) in patients receiving programmed hemodialysis (PHD).Material and methods This study included 74 patients (men, 64.8 %) older than 18 years receiving PHD. Data were processed using mean values of standard biochemical indexes for 16 months. NT-proBNP level was measured and transthoracic echocardiography (EchoCG) and bioimpedancemetry were performed at the time of inclusion into the study. Cumulative incidence of CVE for 16 months was evaluated in patients with different levels of NT-proBNP (quartile 1: &lt;1127 pg/ml; quartile 1-4: 1127-3210 pg/ml; quartile 4: &gt;3210 pg/ml) using the Kaplan-Meier method. For assessment of NT-proBNP as a CVE predictor, receiver operational characteristic curves (ROC curves) were constructed.Results The serum concentration of NT-proBNP was 2114.5 [1127; 3210.4] pg/ml. During 16 months, CVE were observed in 25.6 % of patients. The risk of CVE increased with increasing NT-proBNP quartile in the analysis of Kaplan-Meier curves (Log-Rank test, p=0.032). In this process, CVE did not develop in patients with NT-proBNP concentrations lower than 1127 pg/ml. The ROC analysis demonstrated a good predictive value of NT-proBNP (p=0.006, AUC 0.71, 95 % CI: 0.59-0.83). The optimum cut-off threshold of the NT-proBNP level predictive of CVE was 2093 pg/ml (sensitivity, 84.2 %, specificity, 58.2 %). CVE developed in patients with greater values of volumetric myocardial parameters, indirect signs of hyperhydration (higher predialysis sodium level and pulmonary artery systolic pressure), smaller volumes of substituate per dialysis procedure, and left ventricular systolic dysfunction (p&lt;0.05).Conclusion In patients receiving programmed extracorporeal therapy, the serum concentration of NT-proBNP was considerably higher than mean values in the general population. Apparently, serum NT-proBNP concentrations in the range of 1127-2093 pg/ml can be used as a predictor for a high risk of CVE in the dialysis population. Pronounced structural alterations of the myocardium, left ventricular systolic dysfunction, and hyperhydration are the factors that provide development of CVE on PHD. Large volumes of the PHD substitution solution are associated with a lower incidence of CVE in the dialysis population.

Cumulative incidence of cardiovascular events under tamoxifen and letrozole alone and in sequence: a report from the BIG 1-98 trial.

Compared to tamoxifen, adjuvant treatment with aromatase inhibitors improves disease outcomes of postmenopausal women with hormone receptor-positive early breast cancer. In the international, randomized, double-blind BIG 1-98 trial, 8010 women were randomized to receive tamoxifen, letrozole, or sequential use of the agents for 5years. With a focus on switching between agents, we investigated cardiovascular events over the entire 5-year treatment period. Of the 6182 patients enrolled, 6144 started trial treatment and were included in this analysis. Adverse events occurring during study treatment until 30days after cessation were considered. Eight cardiovascular event types were defined. Cumulative incidence of events were estimated using the Kaplan-Meier method, without consideration for competing events. Multivariable Cox models estimated hazard ratios (HR) with 95% confidence intervals (CI) for pairwise comparisons of treatment arms. While on study treatment, 6.5% of patients (n = 397) had any cardiac events reported; for 2.4%, the event was grades 3-5, of which 11 (0.2%) were grade 5. Letrozole monotherapy was associated with higher risk of grade 1-5 ischemic heart disease (HR = 1.81; 95% CI, 1.06-3.08) compared with tamoxifen monotherapy. Patients assigned sequential tamoxifen →letrozole (HR = 1.59; 95% CI, 0.92-2.74) or sequential letrozole → tamoxifen (HR = 1.20; 95% CI, 0.68-2.14) showed a lesser degree of risk elevation. Patients assigned to tamoxifen-containing regimens had significantly higher risk of grade 1-5 thromboembolic events (tamoxifen monotherapy HR = 2.10; 95% CI, 1.42-3.12; tamoxifen → letrozole HR = 1.96; 95% CI, 1.32-2.92; letrozole → tamoxifen HR = 1.56; 95% CI 1.03-2.35) as compared with patients assigned letrozole alone. When initiating or switching between adjuvant endocrine treatments in postmenopausal patients, age and medical history, with special attention to prior cardiovascular events, should be balanced with expected benefit of the treatment.

The Authors' Reply: Tacrolimus Trough Concentrations After Liver Transplantation: Back to the Future.

The authors thank Dr Rodríguez-Perálvarez for initiating this valuable discussion on our article. We strongly agree with the authors that minimizations strategies are required to reduce the side effects associated with calcineurin inhibitors (CNI) exposure, and our results should not be interpreted as an encouragement to increase immunosuppression (IS) during the early posttransplant period. We deliberately referred to the first 15 days of CNI exposure (not minimization) as a poor tool in predicting long-term adverse events, at least in our population. We concluded that “the effect of early CNI exposure is possibly limited to early posttransplant outcomes and that other factors developing over time have possibly a greater impact on long-term events.”1 Indeed, and as an example, we as well as others have clearly shown the impact of additional variables, such as Framingham score or cumulative doses of CNI overtime on long-term outcomes.2,3 We understand the concerns of the authors regarding the subgroup analysis of patients immunosuppressed with tacrolimus (TAC); indeed, these types of analyses should always be interpreted with caution. We therefore additionally conducted a Bayesian model to further estimate the distribution of IS levels considering a confidence interval (CI) between 0.8 and 1.4 as clinically relevant. The area under the curve obtained of 0.81 highlights that, in our cohort, the first 15 days of CNI levels had no impact on long-term survival or graft loss with an 80% probability. Though we also agree with the authors that mean TAC levels may better reflect peaks of TAC, we also believe that predicting the lifetime events of a transplant patient by 1 TAC peak during the first 15 days is likely an overestimation of the potential toxicities of CNI. Furthermore, it is known that CNI levels during the first 15 days post–liver transplantation are extremely variable as shown in Figure S1 (SDC, https://links.lww.com/TP/B854) of the article.1 In that sense, using median levels of CNI, probably more consistent with their real exposition, is a better approach for understanding the real impact of early IS. Moreover, similar results were achieved regardless of the statistical approach used (mean versus median levels, sensitivity analysis). As highlighted by Rodríguez-Perálvarez, there may be competing risks for particular outcomes such as cardiovascular events; thus, we additionally performed a competing risk analysis for cardiovascular events taking into consideration mortality without finding any association between early IS exposition and cardiovascular events (hazard ratio = 1.229, CI 95% = 0.630-2.398, P = 0.489; hazard ratio = 0.944, CI 95% = 0.478-1.864, P = 0.867, comparing high versus low and optimal IS, respectively, see Figure 1).Figure 1.: Competing risk regression for cardiovascular disease: the cumulative incidence of cardiovascular events comparing high vs low and optimal immunosuppression was not significantly different taking into consideration mortality as competing risk factor.Finally, we would like to highlight the current difficulties in defining optimal IS or minimization strategies given the lack of adequate tools that provide accurate measurement of the net status of IS in a given patient.4,5 Such tools have long been considered the holy grail in immunology and organ transplantation.

Static intra-access pressure ratio and cardiovascular events in patients undergoing haemodialysis

Static intra-access pressure ratio (SIAPR) measurement, using haemodialysis machine transducers, is the vascular access surveillance method in patients undergoing haemodialysis. However, little is known about the relationship between the SIAPR and arterial stiffness, and the clinical usefulness of the SIAPR in predicting cardiovascular events. A total of 209 patients undergoing maintenance haemodialysis were evaluated. The SIAPRs ranged from 0.01 to 0.52 (median: 0.23). When the patients were divided into two groups according to their median of SIAPR, the incidence of previous cardiovascular disease, E/E′ ratio, and brachial-ankle pulse wave velocity were significantly higher in the patients with SIAPRs of ≤0.23 than in those with SIAPRs of >0.23. Conversely, patients with worse comorbid status had a lower SIAPR than patients without it. In the Kaplan-Meier analysis, the cumulative incidence of cardiovascular events was significantly higher in the patients with SIAPRs of ≤0.23 than in those with SIAPRs of >0.23 (P < 0.001). In the multiple Cox regression analysis, an increase in the SIAPR was associated with a reduced risk for cardiovascular events [hazard ratio: 0.36, 95% confidence interval: 0.21–0.60, P = 0.001]. Therefore, a low SIAPR related with arterial stiffness was a predictor for cardiovascular events.