Cox Proportional Hazards Regression Models Research Articles

Residual cardiovascular risk in patients with acute coronary syndromes: from hs-CRP and LDL-C to JCAD

Abstract Background Patients with a recent acute coronary syndrome (ACS) remain at high residual cardiovascular risk to which cholesterol, inflammation, and yet-to-be-identified pathways jointly contribute (1). The novel Junctional Protein Associated with Coronary Artery Disease (JCAD) protein drives incident cardiovascular events via pathways, among them fibrinolysis, that act independently from lipid metabolism and inflammation (2). Purpose Whether circulating JCAD provides predictive utility over and above established risk factors among ACS patients at residual lipid risk (RLR), residual inflammatory risk (RIR), or both (RILR), remains unknown. Methods Among patients participating in the multicentre SPUM-ACS study, patients at RLR (on-statin LDL-C ≥70.0 mg/dl), RIR (on-statin hs-CRP ≥2.0 mg/l) or both (RILR; on-statin LDL-C ≥70.0 mg/dl and CRP ≥2.0 mg/l),(1,3) and propensity-score matched (PSM) controls were identified, and the contributions of plasma hs-CRP, LDL-C and JCAD toward recurrent major adverse cardiovascular events (MACE; defined as a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) were studied by fitting uni- and multivariable-adjusted Cox proportional hazard regression models. Results Patients at RLR, RIR, or both (RILR) were at higher MACE risk compared to controls (hazard ratio [HR] per log2 increase, 1.51; 95% confidence interval (CI), 1.05-2.17; HR, 1.78; 95% CI, 1.23-2.58; and HR 1.75; 95% CI, 1.12-2.74; Figure 1). Among those at RLR, MACE risk increased with increasing levels of hs-CRP and JCAD, respectively, in uni- (HR, 1.17; 95% CI, 1.06–1.30; HR, 1.29; 95% CI, 1.03-1.62) and multivariable-adjusted models (adjusted [a]HR, 1.16; 95% CI, 1.03–1.30; aHR, 1.27; 95% CI, 1.01-1.60), whereas no association of LDL-C and future MACE risk was noted. Similarly, among patients at RIR, MACE risk increased by 1.28-fold per log2 increase in plasma JCAD (HR, 1.28; 95% CI, 1.03–1.59), which prevailed in multivariable-adjusted models accounting for potential confounders (aHR, 1.31; 95% CI, 1.04–1.65). In ACS patients at both residual inflammatory and lipid risk, MACE risk associated almost linearly with increasing JCAD levels (HR, 1.45; 95% CI, 1.09–1.92), independently of potential confounders (aHR, 1.47; 95% CI, 1.11–1.97). Meanwhile, no association of LDL-C or hs-CRP with MACE risk was identified among these high-risk patients (Figure 2). Conclusions ACS patients at RIR, RLR, or both are at high ischaemic risk, with JCAD ranking among the top predictors of MACE across the broad spectrum of residual risk. Our data highlight the importance of novel pathways to address residual cardiovascular risk, with JCAD ranking among most promising candidates.

Mortality rate of percutaneous coronary interventions in st-segment elevation myocardial infarction patients under the public health insurance schemes of thailand

Abstract Background ST-elevation myocardial infarction (STEMI) presents a critical public health challenge internationally, including in Thailand. Currently, standard therapeutic interventions, particularly primary percutaneous coronary interventions (pPCI), are administered to Thai citizens. However, selected healthcare systems restrict access to specific pharmaceuticals and medical devices, causing inequalities in the quality of medical care amongst different healthcare systems. Such inequalities have the potential to significantly impact the quality of life of patients, particularly in the long term. Purpose The primary objective is to compare mortality rates within one year of STEMI patients after treatment with pPCI among the public health insurance schemes of Thailand. The secondary objective is to study prognostic determinants for one-year mortality rates among patients diagnosed with STEMI who have undergone pPCI. Methodology This study is a single-centre retrospective analysis of patients with STEMI treated with pPCI. It involves patients utilising various state health insurance schemes in Thailand from 1 January 2010 to 31 December 2020. Data collection occurred through the hospital's computerised management system and the registration administration office of the Department of Provincial Administration. The data analysis employed the Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazards regression modelling method. Results The study involved 1,077 patients, categorised into three groups based on their state health insurance: Universal Health Coverage (UC) (546 patients, 50.7%), Social Security System (SS) (199 patients, 18.5%), and Civil Service Reimbursement (CS) (332 patients, 62.6%). The one-year mortality rates in these groups were 10.57%, 4.21%, and 6.47%, respectively (p=0.010). In the unadjusted model, the SS group showed a lower risk of one-year mortality rate (HR 0.38, 95% CI 0.18-0.80, p=0.011), and the CS group also demonstrated a lower risk (HR 0.59, 95% CI 0.35-0.99, p=0.047) compared to the UC group. In the adjusted model, only the CS group significantly reduced the risk of one-year mortality. Other factors that affected one-year mortality were age ≥65 years, a Killip score of 3-4, pre-discharge prescription of angiotensin-converting enzyme inhibitors, occlusion in the left anterior descending artery, and pericardial effusion. Conclusion Healthcare schemes play a significant role in influencing one-year mortality rates among STEMI patients treated with pPCI. The use of civil service reimbursement is a protective factor for the one-year mortality rate in STEMI patients. This information would be crucial for developing strategies and programs to aid healthcare policymakers at both regional and international levels in reducing morbidity and mortality.

One-year prognosis difference of MINOCA versus MI-CAD in developing countries: insights from the Moroccan experience

Abstract Introduction The debate remains open as to the difference in prevalence of mortality and occurrence of acute events in patients with Myocardial infarction with non-obstructive coronary arteries (MINOCA) and others with Myocardial infarction with coronary arteries disease (MI-CAD) (1). Purpose We carried out an analysis of the clinical characteristics and one-year prognosis of MINOCA versus MI-CAD. Methods We conducted a prospective study for patients admitted for Acute coronary syndrome (ACS) during 2-years, to analyze the clinical and prognostic characteristics of patients with MINOCA versus MI-CAD. We defined 1-year all-cause mortality as the primary outcome, and the secondary outcome as a composite of 1-year readmission for myocardial infarction or acute heart failure (AHF). The primary and secondary outcomes was studied using a Cox proportional hazards regression model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for variables described in the literature. Results Our study included 1077 patients, 95.3% with MI-CAD and 4.7% with MINOCA. At admission, 71.1% patient were diagnosed STEMI and 28.9% with NSTEMI. The difference between the two groups was found on age (p<0.001), hypertension, diabetes with consecutive p-values of 0.007 and 0.001, as well as Ejection fraction (p<0.001). For the outcomes studied, we found, firstly before adjustment, that patients in the MINOCA group had a better prognosis than the MI-CAD group, for all-cause 1-year mortality (HR=0. 442; 95%CI 0.227-0.760; p=0.041) with a significant difference in the Kaplein Meier survival analysis with a log-rank test (p-value =0.02) (Figure 1), and a lower risk of readmission for ACS (HR=0.297; 95%CI 0.316-0.821; p=0.034), as well as for readmission for AHF (HR=0.555; 95%CI 0.329-0.836; p=0.045) also with a significant difference between the two groups in the Kaplein Meier analysis with consecutive log-rank test p-values of 0.033 and 0.035 (Figure 2). After adjustment for age, arterial hypertension, diabetes, active smoking, EF<40%, proximal LAD or LM as culprit artery, TIMI 0-I flow, CRP >300mg and cardiogenic shock during hospitalization, the results remained significantly in favor of a better prognosis for MINOCA: (HR=0. 672; 95%CI 0.376-0.872; p=0.003) for 1-year all-cause mortality, (HR=0.301; 95%CI 0.482-0.879; p=0.012) for readmission for ACS and finally (HR=0.604; 95%CI 0.309-0.812; p=0.039) for readmission for AHF. Conclusion Despite the ambiguity in the genesis of MINOCA, the short- and long-term prognosis of these patients remains generally favorable.Figure 1.Figure 2.

Risk of recurrent ischaemic events in ACS patients with baseline LDL-C below guideline-recommended thresholds: insights from the prospective SPUM-ACS study

Abstract Introduction The 2023 European Society of Cardiology (ESC) guidelines recommend intensive low-density lipoprotein cholesterol (LDL-C) reduction for patients with acute coronary syndromes (ACS), adding ezetimibe and/or proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) to achieve recommended target goals (LDL-C<55 mg/dL). Purpose This population-based, real-world study aimed to examine cardiovascular (CV) events in ACS patients with baseline LDL-C levels below current guideline thresholds. Methods ACS patients admitted to four Swiss University Hospitals and enrolled in the multicenter SPUM registry (NCT 01000701) between 2009 and 2017 were followed prospectively until 1 year. The composite primary endpoint was major adverse cardiac and cerebrovascular events (MACCE); i.e., non-fatal stroke, myocardial infarction (MI), and death) at 1 year. Multivariable-adjusted Cox proportional hazard regression models were fit to estimate ischaemic risk among those with LDL-C<55 mg/dL. Results Out of 4’787 ACS patients, 226 patients (4.7%) had baseline LDL-C<55 mg/dL. These patients were older (69.7±11.3 vs 63.4±12.4, p<0.001), more frequently male (20.8%vs 15.9%, p<0.001), had more often traditional CV risk factors (all p<0.001) and were more likely to have a complex history of CV disease, such as previous MI (37.2% vs 10.9%, p<0.001), prior percutaneous (47.8% vs 13.2%, p<0.001) or surgical (15.0% vs 3.5%, p<0.001) coronary revascularization. Inflammatory biomarkers were also higher (hs-CRP, 30.1±63.6 vs 10.7±25.8 mg/L), with most patients being on high-dose statin therapy (82.4% vs 38.7%, p<0.001). At 1 year, patients with LDL-C<55 mg/dL had a higher rate of MACCE (16.4% vs 7.0%, p<0.001), with individual components of the primary endpoint occurring more frequently among these patients (all p<0.001), except for a numerical increase in CE (2.7% vs 1.7%, p=n.s.), as shown in the figure (Panel A). The enhanced MACCE risk persisted after adjustment for potential differences in baseline characteristics, with a 51% (adj. HR 1.51, CI95% 1.05-2.17, p=0.026) increase in MACCE (Panel B). Diabetes, low eGFR and high hs-CRP levels remained independent predictors of MACCE in patients with low baseline LDL-C (all p<0.001). Conclusions Our real-world data confirm that even ACS-patients reaching currently recommended LDL-C thresholds have a substantial incidence of recurrent CV events. These findings reinforce the opportunity for lipid-lowering therapy intensification in high-risk patients to levels below guideline-recommended threshold in order to further reduce CV risk.Event-risk according to baseline LDL-C

The association between endogenous erythropoietin levels and the risk of heart failure in a Chinese community-based population

Abstract Background Patients with heart failure (HF) often have elevated endogenous erythropoietin (EPO) levels, which are associated with disease severity and prognosis. Previous studies have indicated that in the special population elevated endogenous EPO levels are associated with HF and cardiovascular death. However, whether endogenous EPO levels are associated with the risk of HF in the general population remains to be elucidated. Purpose Our study aims to investigate the association between endogenous EPO levels and the risk of HF admission in the general population. Methods We conducted a prospective cohort study on subjects from a Beijing community in China who had no history of stroke or myocardial infarction. Endogenous EPO levels were measured at baseline for all participants. The endpoint of interest was admission with HF. Cox proportional hazard regression models were used to analyze the relationship between endogenous EPO levels and the occurrence of the endpoint. Results A total of 4870 participants were included. Among all participants, the mean (±SD) age was 56.72 ± 8.78 years, with 1802 (37.0%) being men. The median (interquartile range, IQR) EPO level was 13.19 (9.47-18.20) IU/L. During a mean 9.57-year follow-up, a total of 176 (3.6%) subjects experienced heart failure. Subjects were grouped in quintiles according to baseline endogenous EPO levels. Higher and lower endogenous EPO levels were both associated with increased risk of HF (Figure 1A). The Kaplan–Meier curves showed significant differences in cumulative hazards of heart failure among EPO quintiles (log-rank test: P＜0.05) (Figure 1B). After adjusting for covariates, including demographics, traditional risk factors for cardiovascular disease, renal function, and hemoglobin levels, and using the middle quintile (Q3) (11.72-14.94IU/L) of EPO levels as a reference, we found that the highest quintile (Q5) (>19.86 IU/L) was associated with a 159% increased risk of HF admission (HR 2.59, 95% CI 1.57-4.28, P = 0.0002). Similarly, the lowest quintile (Q1) (<8.66 IU/L) was associated with a 94% increased risk (HR 1.94, 95% CI 1.11-3.41, P = 0.0210) (Table 1). Conclusion There exists a "U-shaped" relationship between endogenous EPO levels and HF admission in the general population. Both higher and lower endogenous EPO levels were associated with an increased risk of HF admission in the community population. These findings differ from previous studies, so further research may be needed to explore the underlying pathophysiological mechanisms of endogenous EPO and HF.

Inflammation and long-term outcomes after first-time direct current cardioversion for atrial fibrillation: a nationwide register study

Abstract Background Emerging evidence suggests that the pathogenesis of atrial fibrillation (AF) is affected by inflammatory processes which contribute to structural and electrical remodeling of the atria, creating a substrate for arrythmia. Aim To assess whether inflammation measured by C-reactive protein (CRP) is associated with readmission for direct current (DC) cardioversion, ablation, heart failure or stroke after discharge from 1st time DC cardioversion. Methods This nationwide retrospective cohort study included patients undergoing 1st DC cardioversion between 2011 and 2018. Exclusion criteria were death within one day of cardioversion and no available CRP at baseline. Primary outcome was readmission for DC cardioversion of AF. Secondary outcomes were AF ablation, new admission of stroke, new admission of heart failure (HF), and all-cause death. Absolute risk rates (ARR) of outcomes were calculated for patients with available 1-year follow-up data. CRP 20 mg/L was chosen as cutoff to establish a clinically relevant borderline for inflammation. The association between baseline CRP and outcome was assessed in Cox proportional hazards regression models with a follow-up period starting from 1st DC cardioversion, ending no later than 31st of December 2018, for the entire study population (n=9,977). Results After exclusion criteria the study population consisted of 9,977 patients Mean age for CRP > 20mg/L: 66.8 (IQR: 60.5-74.2). Mean age for CRP < 20mg/L 68.9 (IQR: 62.9-75.9)(p<0.001). In total, 68.9% were male and the most frequent comorbidities included hypertension (57.3%), ischemic heart disease (25.1%), HF (20.6%), and history of stroke (7.1%). Patients with available CRP measurement and 1yr follow up was 7,764. Compared to patients with low CRP (<20 mg/L), patients with elevated CRP (>20mg/L) had a higher 1-year ARR of HF, and all cause death (p<0.001). Compared to patients with low CRP, patients with elevated CRP had a lower 1-year ARR of all-ablation and new DC cardioversion (p<0.001), (Table 1). CRP > 20mg/L was associated with lower risk for new DC cardioversion (HR 0.72, 95% CI: 0.64-0.82, p<0.001). However, in patients <75 years of age with CRP > 20mg/L at baseline had an increased risk of stroke after multivariable adjustments (HR 1.92, 95% CI: 1.10-3.35; p = 0.02) (Fig.1), while CRP > 20 mg/L was not associated with an increased risk of stroke in patients > 75yrs of age (Cox regressions estimates) (p for interaction = 0.03). Conclusion However, elevated CRP was associated with an increased risk of stroke in patients <75 years of age, even after multivariable adjustments. These results suggest that CRP may not be a reliable predictor of readmission for DC-cardioversion, especially in older individuals, but might be a potential risk stratification tool in identifying AF patients at higher risk of stroke in young individuals. We suspect this is due to the population with elevated CRP has more comorbidities and are older.

Cardiovascular outcomes in acute coronary syndrome patients with cancer: a statewide population-linkage study

Abstract Background Advances in oncology treatment have led to an increase in the number of cancer survivors. As a result, the number of acute coronary syndrome (ACS) patients with cancer is increasing and the outcomes of these patients are not well described. Purpose This study aimed to examine revascularisation strategies and all cause and cardiovascular death in ACS patients with and without cancer. Methods Hospitalised patients in New South Wales, Australia, from July 2006 to December 2020 with a primary diagnosis of ACS were identified from the statewide Admitted Patient Data Collection database. Patients were stratified into those with or without a history of cancer (non-melanoma skin cancers excluded). Propensity scoring matching (PSM) for the variables of age, gender and cardiovascular risk factors was performed with each cancer patient matched to two non-cancer patients. Cox proportional hazards regression model was used to evaluate the hazard ratios of all-cause mortality between individuals with a history of cancer in the 5 years preceding their hospital admission, and those without. Additionally, Fine-Gray competing risk analysis was performed for cardiovascular death with non-cardiovascular mortality as the competing event. Results During the study period, 193,848 patients were admitted with ACS. 12,543 patients had a history of cancer and were PSM to 25,085 patients without cancer. The median age was 75 (Q1-Q3 67-82) years with 69% male and hypertension the most prevalent risk factor (55%) (Table 1). ACS patients with cancer had clinically comparable, rates of percutaneous revascularisation (36 vs 37%, p=0.07) and coronary artery bypass grafting (11 vs 13%, p<0.001) with ACS patients without cancer. During a median follow up of 8.6 (95% CI 8.4-8.8) years, ACS patients with a history of cancer had a significant higher risk of all cause death (HR 1.42 95% CI [1.38-1.46]) and cardiovascular death (SHR 1.14 [1.11-1.18]). The cumulative incidence function demonstrated cardiovascular death in those with a cancer history occurred in 20% by approximately 1.4 years follow up compared to 2.5 years in those without cancer (Figure 1). Conclusion ACS patients with cancer have a higher risk of all cause death and cardiovascular death compared to those without a history of cancer with clinically comparably revascularisation rates. Further studies to determine the cause of increased cardiovascular death in ACS patients with cancer are required.Figure 1

Systolic blood pressure time in target range and cardiovascular disease and premature death

Abstract Background Time-in-target range (TTR) for systolic blood pressure (SBP) independently predicts cardiovascular outcomes. However, there are limited research based on real-world data. Purpose To estimate SBP-TTR associated with cardiovascular disease (CVD) and premature death among the employed individuals with hypertension. Methods This study is based on the Kailuan cohort. As part of the Kailuan study, a workplace-based hypertension management programme was initiated in 2009 for employed people with hypertension. The TTR was defined as 120 to 140 mmHg according to the current guidelines, and in the sensitivity analyses it was further defined as 110 to 130 mmHg. TTR was estimated over the first 6 months of follow-up using linear interpolation. The association between SBP-TTR with CVD, premature CVD and premature death was estimated using adjusted Cox proportional hazards regression models to adjust for multiple confounders. Results A total of 9552 hypertensive participants were included. A one standard deviation increase in SBP-TTR is associated with a 19% reduction in the risk of CVD (HR:0.81; 95%CI: 0.74 to 0.88), a 24% reduction in the risk of premature CVD (HR:0.76; 95%CI: 0.67 to 0.86), and a 17% reduction in the risk of premature death (HR:0.83; 95%CI: 0.74 to 0.92). When SBP-TTR is redefined as 110-130 mmHg, a one standard deviation increase in SBP-TTR is associated with a 23% reduction in the risk of CVD (HR:0.77; 95%CI: 0.70 to 0.84), a 30% reduction in the risk of premature CVD (HR:0.70; 95%CI: 0.60 to 0.81), and a 27% reduction in the risk of premature death (HR:0.73; 95%CI: 0.66 to 0.80). These associations were independent of SBP-mean and SBP-SD. Subgroup analysis results indicate that SBP-TTR contributes to a reduction in the risk of premature death in individuals with a high cardiovascular risk score. Conclusions SBP-TTR was statistically associated with a decreased risk of CVD, premature CVD and premature death. Intensifying blood pressure control measures can further increase cardiovascular benefits.

Ultra-processed food consumption and risk of coronary heart diseases: UK Whitehall II cohort study

Abstract In recent decades, ultra-processed foods (UPFs) intake has increased drastically, sparking concerns about their potential impact on cardiometabolic diseases. However, large-scale cohort studies tracking UPF consumption at multiple time points remain limited. This study explores the prospective association between repeated measures of UPF intake and the risk of coronary heart disease (CHD), along with its secondary endpoints, within the UK Whitehall II study. The analytical sample tracked 7,138 midlife British participants without CHD from baseline. UPF consumption was measured using validated food frequency questionnaire (127 items) and classified by the NOVA system during three phases: 1991/1994 (phase 3), 1997/1999 (phase 5), and 2002/2003 (phase 7). This study assessed the onset of CHD and its secondary endpoints, including CHD and all-cause mortality, through medical exams and hospital records up to 2016 and 2021, respectively. Cox proportional hazards regression models adjusted for socio-demographics, lifestyle factors and total energy intake were used to explore the prospective association between cumulative average UPF intake (in quintiles) and CHD outcomes. During a median follow-up of 13 and 19 years, 589 cases and 1,314 deaths were documented. In multivariable adjusted cox models, the highest UPF consumption quintile versus the lowest quintile was associated with higher CHD incidence [HR:1.26; 95% Confidence Interval (CI): 1.02-1.55; p = 0.03]. Additional adjustment of total energy intake increased the CHD risk by 28% [HR:1.28; 95% CI: 1.03-1.58; p = 0.02]. No significant relationships were found between cumulative average UPF intake and CHD or all-cause mortality. In UK midlife adults, higher UPF intake is prospective associated with increased CHD risk. Although additional research is warranted, these findings emphasize the importance of public awareness and food policy interventions to reduce UPF intake for alleviating the population burden of CVD. Key messages • Our study suggests the need for increased efforts to implement population wide strategies on regulating food processing, such as taxation and front of package warning labelling of UPF. • Our study emphasizes UPF’s role in cardiovascular prevention, highlighting the need for nutrition counseling on UPF consumption for those at risk of CVD.

Obesity paradox exists in super elderly patients with heart failure

Abstract Background Aging and obesity are two global concerns in public health. As obesity is associated with several metabolic disorders, it is a well-known risk factor of heart failure (HF). However, several studies have suggested that obesity may have paradoxical survival benefits in patients with HF. Therefore, the aim of this study was to investigate whether the obesity paradox exists in super elderly patients with HF in Japan. Methods A total of 4,292 patients from our hospital HF registry were divided into four age subgroups: (A) less than 65, (B) elderly 65-74, (C) high elderly 75-84, (D) super elderly ≥85. The primary endpoint was the all-cause death within 1-year after discharge. Results At baseline, the proportion of men in each group was 42-76%, the mean left ventricular ejection fraction was 49-61%, the average of N-terminal pro-B-type natriuretic peptide was 1972-2944 pg/ml, and the mean body mass index (BMI) ranged 21-25 kg/m2. Patients with higher BMI were more common in the younger age group, while those with lower BMI were more common in the older age group. Cubic spline curves of Cox proportional hazard regression models demonstrated an inverse relationship between BMI and mortality (Fig. 1). Lower BMI was associated with higher all-cause mortality in all ages, although this association was attenuated at the young age, and pre-obesity (25–29.9 kg/m2) was associated with the greatest survival benefit. Meanwhile, the impact of underweight (<18.5 kg/m2) was stronger super elderly subjects, a one-unit increase in BMI was associated with a 10.3% decrease in the hazard ratio of death (P=0.021). Kaplan-Meier curves for all-cause mortality also showed that lower BMI was associated with higher all-cause mortality in all groups, and the differences were statistically significant in Groups B, C, and D (Fig. 2). Conclusion Our study suggested the existence of the obesity paradox among HF patients in super elderly. Mildly overweight may be beneficial at old age with HF.

Red-cell omega-3 fatty acids associate with increased hippocampal volume and superior longitudinal cognition in atrial fibrillation

Abstract Background Atrial fibrillation (AF) is associated with cognitive impairment and dementia. Omega-3 Fatty Acids (n-3 FAs) have anti-thrombotic, anti-inflammatory and anti-oxidative properties; however, their neuroprotective effects remain controversial. Here, we report the association of n-3 FAs with both structural (hippocampal volume) and functional (cognition) readouts in a large cohort of AF pts. Purpose a) To determine the association of n-3 FAs and left and right hippocampal volume at baseline in AF pts. b) To assess the predictive value of HV and n-3 FAs for the risk of cognitive impairment after a 7-year follow-up period. Methods This prospective ongoing multicenter Swiss Atrial Fibrillation study (Swiss-AF) included 2,359 pts with documented AF and baseline red-cell n-3 FAs levels, measured by gas chromatography and mass spectrometry. Hippocampal volume (HV) and segmentation based intracranial volume (ICV) were analyzed by FreeSurfer's (v 7.4.0) subregion segmentation module and Sequence Adaptive Multimodal SEGmentation from brain MRI in 1,736 pts. Detailed neurocognitive assessments in pts at baseline and follow up periods were performed. We used mixed-effect linear regression models to determine the association of n-3 FAs and HV. For conversion to cognitive impairment (defined as MoCA score < 26), we performed cox-proportional hazards regression model. Two adjustment models were applied as described in the figures. Results Patients with AF (mean age, 73 years old [±8.5 SD]; 157 women [27%]) with 9569 cognitive evaluations (mean follow-up, 3.6 years [±2.3 SD]) were assessed. At baseline, we observed statistically significant associations between total n-3 FAs levels (EPA + DHA + ALA + DPA) and individual n-3 FAs (EPA, DHA, DPA) with increased HV after adjustment for ICV and other covariates (Fig1A, 1B). After all adjustments, EPA remained associated with both bilateral HV and right HV. Furthermore, we observed a significant association between HV and neurocognitive assessments, as measured both in global (MoCA, CoCo) and specific tests (TMT-A, TMT-B, DSST, SF) (Fig1C). Over time, quartile 4 (Q4, highest n-3) compared to quartile 1 (Q1, lowest), had a 16% lower risk of cognitive impairment (HR, 0.84 [CI 0.75-0.93]; P=0.001) for total n-3 FAs and even 30% lower specifically for EPA (HR, 0.7 [CI 0.63-0.78]; P<0.001). The risk of cognitive impairment was 47% lower (HR, 0.53 [CI 0.45-0.63]; P<0.001) when the highest HV Q4 was compared to lowest HV Q1 (Fig2A). In combination, the highest quartile of bilateral HV and EPA demonstrated an increased probability of being cognitive impairment-free and they had a 72% lower (HR, 0.28 [0.18-0.43]; P<0.001) risk of cognitive impairment (Fig2B). Conclusions 1. Red cell n-3 FAs levels are associated with higher HV in AF pts. 2. Higher baseline levels of n-3 FAs, particularly of EPA, are associated with both an increased HV and a decreased risk of cognitive impairment after 7 years follow up.

Lack of incremental prognostic value of triglyceride glucose index beyond coronary computed tomography angiography features for major events

This study was aim to determine the prognostic value of triglyceride-glucose (TyG) index and coronary computed tomography angiography (CTA) features for major adverse cardiovascular events (MACE). In addition, we investigate the incremental prognostic value of TyG index beyond coronary CTA features in patients with suspected or known coronary artery disease (CAD). The present study ultimately includes 3528 patients who met the enrollment criteria. The TyG index was calculated based on measured levels of triglycerides and fasting blood glucose. Primary combined endpoint consisted of MACE, which defined as myocardial infraction (MI), all-cause mortality and stroke. Three multivariate Cox proportional hazard regression models were performed to assess the association between TyG index and MACE. C-statistic was performed to assess the discriminatory value of models. 212 (6.0%) patients developed MACE during a median follow-up of 50.4 months (IQR, 39.4–55.1). TyG index remained to be a significantly and independent risk factors for predicting MACE after adjusting by different models (clinical variables alone or plus coronary CTA features) in multivariable analysis. Both the addition of TyG index to clinical model plus Coronary Artery Disease Reporting and Data System (CAD-RADS) and to clinical model plus CAD-RADS 2.0 slightly but not significantly increased the C-statistic index (0.725 vs. 0.721, p = 0.223; 0.733 vs. 0.731, p = 0.505). TyG index was associated with an increased risk of MACE. However, no incremental prognostic benefit of TyG index over CAD-RADS or CAD-RADS 2.0 was detected for MACE in patients with suspected or known CAD.

Adjuvant Modified FOLFIRINOX for Resected Pancreatic Adenocarcinoma (PDAC): Clinical Insights and Genomic Features from a Large Contemporary Cohort.

Adjuvant mFOLFIRINOX (mFFX) is standard of care for fit individuals with resected pancreatic ductal adenocarcinoma (PDAC). There are limited data on adjuvant mFFX outcomes outside clinical trials. Institutional databases queried to identify patients with resected PDAC who received ≥1 dose adjuvant mFFX. Primary endpoints: recurrence free survival (RFS), overall survival (OS). Secondary endpoints: clinical factors, genomic features associated with outcomes. RFS and OS were estimated with Kaplan-Meier. Cox proportional hazards regression model was used to associate clinico-genomic features correlated with survival outcomes. N = 147 identified between 01/2015-01/2023. Median age: 67 years; N = 57 (39%) >70 years. Unfavorable prognostic features: N = 52 (36%) N2 nodal status, N = 115 (78%) lymphovascular invasion), and N = 133 (90%) perineural invasion. Median time from surgery to start mFFX: 1.78 months (m) (IQR 1.45, 2.12). N = 124 (84%) completed 12 doses; N = 98 (67%) stopped oxaliplatin early for neuropathy (median 10 doses; range 4-12). Further dosing characteristics are summarized in Supplementary Table 3. With median follow up of 35.1 m, median RFS (mRFS) 26 m (95% CI 19, 39) and median OS (mOS) not reached. For >70 cohort, mRFS 23 m (95% CI 14, NR) and mOS 51 m (95% CI 37, NR). mFFX started <8 weeks from resection associated with improved RFS (HR 0.62; 95% CI 0.41, 0.96; p = .033) and OS (HR 0.53; 95% CI 0.3, 0.94; p = .030). KRAS mutation and whole genome doubling trended to shorter RFS and OS. Homologous recombination deficiency status did not confer improved survival outcomes. Adjuvant mFFX is effective and tolerable in resected PDAC in a non-trial setting, including for patients >70 years.

Combined effect of triglyceride glucose-body mass index and hypertension on new-onset stroke: evidence from the China health and retirement longitudinal study

ObjectiveThe aim of this study is to investigate the combined impact of the triglyceride glucose-body mass index (TyG-BMI) and hypertension on the risk of stroke among the middle-aged and older adult population in China.MethodsThis study included 6,922 participants aged 45 and above from the China Health and Retirement Longitudinal Study, utilizing a multivariate Cox proportional hazards regression model to explore the relationship between TyG-BMI, hypertension, and the incidence of new-onset stroke events, as well as conducting Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI) analyses to evaluate the predictive utility of TyG-BMI.ResultsDuring a 7-year follow-up period, a total of 401 stroke events were recorded. Compared to patients with lower TyG-BMI (TyG-BMI &amp;lt; 199.74) levels and non-hypertension, those with elevated TyG-BMI levels and non-hypertension had an adjusted hazard ratio (HR) and 95% confidence intervals (95%CI) were 1.47 (1.05–2.05). The adjusted HR and 95%CI for the group with lower TyG-BMI levels and hypertension was 2.99 (2.17–4.12), and for those with elevated TyG-BMI levels and hypertension, the adjusted HR and 95%CI was 3.49 (2.63–4.62). In a multivariate Cox proportional hazards regression model, the combination of elevated TyG-BMI levels and hypertension, treated as routine variables, was still significantly associated with the risk of stroke. NRI and IDI analyses showed significant improvements in risk prediction with the inclusion of TyG-BMI. Furthermore, in all subgroup analyses conducted, individuals with elevated TyG-BMI levels and hypertension nearly exhibited the highest risk for incident stroke.ConclusionOur study reveals that the combined effect of TyG-BMI and hypertension may increase the risk of incident stroke in the middle-aged and older adult Chinese population. TyG-BMI correlates with comorbid conditions and enhances traditional risk assessment. Future research will require validation through larger sample sizes or diverse populations to further confirm this finding.

What is the optimal range of fasting stress hyperglycemia ratio for all-cause mortality in American adults: An observational study.

To date, no studies have been conducted to assess the impact of fasting stress hyperglycemia ratio (SHR) on all-cause mortality. Therefore, the objective of our study is to investigate the association between SHR and all-cause mortality in a population of American adults. The study population was derived from NHANES data spanning from 2005 to 2018. The exposure variable SHR was derived from fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c%), and the specific calculation formula was as follows: (FBG (mmol/L))/(1.59 × HbA1c (%) - 2.59). The outcome variable was all-cause mortality. A total of 18,457 participants were enrolled in this prospective cohort study. Following a median follow-up period of 90 months, all-cause mortality was observed in 10.32% of the subjects. Cox proportional hazards regression model indicates that there is no significant difference between SHR and all-cause mortality in the fully adjusted model, whether analyzed as a continuous or categorical variable (P for trend > 0.05). Through the 2-piecewise Cox proportional hazards regression model, we have determined that the inflection point of SHR in relation to all-cause mortality is 0.88. It has also been observed that when the value of SHR is on the left side of the inflection point (SHR ≤ 0.88), there is a significant 77% (HR: 0.23; 95% CI: 0.10-0.50) reduction in all-cause mortality for each additional unit increase in SHR. Conversely, when the value of SHR exceeds 0.88, there is a substantial 2.40-fold (HR: 2.40; 95% CI: 1.61-3.58) increase in the risk of all-cause mortality (P for log likelihood ratio test < .001). The subgroup analysis results demonstrate that sex has the potential to modify the association between SHR and all-cause mortality within the population exhibiting SHR ≤ 0.88. The relationship between SHR and all-cause mortality follows a U-shaped pattern, where in the lowest risk of death for the average American adult is observed at an SHR value of 0.88. Furthermore, in men with SHR ≤ 0.88, there is a significant inverse relationship between the increase in SHR and the risk of all-cause mortality.

Association between the triglyceride to high-density lipoprotein cholesterol ratio and cardiovascular diseases in people living with HIV: Evidence from a retrospectively cohort study 2005-2022.

The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel biomarker for metabolic syndrome (MetS), has been validated in the general population as being significantly correlated with cardiovascular disease (CVD) risk. However, its capabilities to predict CVD in people living with HIV (PLWH) remain underexplored. We conducted a retrospective cohort study of 16,081 PLWH who initiated antiretroviral therapy (ART) at the Third People's Hospital of Shenzhen (China) from 2005 to 2022. The baseline TG/HDL-C ratio was calculated as TG (mmol/L) divided by HDL-C (mmol/L). We employed a multivariate Cox proportional hazards model to assess the association between the TG/HDL-C ratio and CVD occurrence, using Kaplan-Meier curves and log-rank tests to compare survival distributions. The increase in prediction risk upon the addition of the biomarker to the conventional risk model was examined through the assessment of changes in net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Nonlinear relationships were investigated using a restricted cubic spline plot, complemented by a two-piecewise Cox proportional hazards model to analyze threshold effects. At the median follow-up of 70 months, 213 PLWH developed CVD. Kaplan-Meier curves demonstrated a significant association between the increased risk of CVD and a higher TG/HDL-C ratio (log-rank P <0.001). The multivariate-adjusted Cox proportional hazards regression model indicated that the CVD hazard ratios (HR) [95% confidence intervals (95% CI)] for Q2, Q3, and Q4 versus Q1 of the TG/HDL-C ratio were 2.07 (1.24, 3.45), 2.17 (1.32, 3.57), and 2.20 (1.35, 3.58), respectively (P <0.05). The consideration of the TG/HDL-C ratio in the model, which included all significant factors for CVD incidence, improved the predictive risk, as indicated by the reclassification metrics (NRI 16.43%, 95%CI 3.35%-29.52, P = 0.014). The restriction cubic spline plot demonstrated an upward trend between the TG/HDL-C ratio and the CVD occurrence (P for non-linear association = 0.027, P for overall significance = 0.009), with the threshold at 1.013. Significantly positive correlations between the TG/HDL-C ratio and CVD were observed below the TG/HDL-C ratio threshold with HR 5.88 (95% CI 1.58, 21.88, P = 0.008), but not above the threshold with HR 1.01 (95% CI 0.88, 1.15, P = 0.880). Our study confirms the effectiveness of the TG/HDL-C ratio as a predictor of CVD risk in PLWH, which demonstrates a significant nonlinear association. These findings indicate the potential of the TG/HDL-C ratio in facilitating early prevention and treatment strategies for CVD among PLWH.

Prognostic potential of standard laboratory parameters in patients with metastatic renal cell cancer receiving first-line immunotherapy

Through their involvement in cancer metabolism, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), γ-glutamyltransferase (GGT) and lactate dehydrogenase (LDH) reflect the tumor burden and thus could have a prognostic potential for patients treated with immune checkpoint inhibitors (CPI). Therefore, this study investigated the prognostic potential of these parameters in a real-world cohort of patients with metastatic renal cell cancer (mRCC) under first-line CPI-based therapy. The retrospective study cohort included 82 mRCC patients treated with CPI-based first-line therapy between 2019 and 2023. Progression-free survival (PFS), overall survival (OS) and response rates were evaluated according to baseline levels and early dynamic changes of ALAT, ASAT, GGT and LDH. Multivariate Cox proportional hazard regression models were generated to identify independent prognosticators for PFS and OS. High baseline levels and non-normalized kinetics of ALAT, ASAT, GGT and LDH were significantly associated with shorter PFS and OS (p < 0.05), which was also reflected by lower response rates. Combining the four parameters at baseline into a 4-Risk-Score resulted in an enhanced prognostic power, as indicated by a higher C-index of 0.693 for OS compared to the individual parameters (≤ 0.663). Patients with all four risk factors present showed the worst PFS and OS. Overall, baseline levels and early kinetics of the four parameters as well as the 4-Risk-Score were identified as independent prognosticators for PFS and OS by multivariate analysis. As standard laboratory parameters, ALAT, ASAT, GGT and LDH are cost-effective and could be easily used either alone or in combination for therapy monitoring of CPI-treated mRCC patients.

No accelerated progression of subclinical atherosclerosis with integrase strand transfer inhibitors compared to non-nucleoside reverse transcriptase inhibitors.

The role of integrase strand transfer inhibitors (INSTI) in the cardiovascular risk of people with HIV is controversial. To assess the association of INSTI to subclinical atherosclerosis progression measured with the carotid intima-media thickness (cIMT). Prospective study in virologically suppressed people with HIV receiving INSTI- or NNRTI-based regimens. cIMT was measured at baseline, 48 and 96 weeks. cIMT progression was analysed both as a continuous and categorical variable, defined as cIMT increase ≥ 10% and/or new carotid plaque. Adjustments through Cox proportional hazard regression and linear mixed models, and propensity score matching were conducted. 190 participants were recruited and 173 completed the 96 week follow-up. 107 (56.3%) were receiving an INSTI-containing, 128 (67.4%) a NNRTI-containing and 45 (23.7%) a NNRTI plus an INSTI-containing regimen. The overall median (IQR) 2-year change of cIMT was 0.029 (-0.041 to 0.124) mm; 87 (45.8%) participants experienced a cIMT increase ≥ 10%, of whom 54 (28.4%) developed a new carotid plaque. Adjusted Cox regression showed no differences between INSTI and NNRTI groups in the categorical 2-year progression of cIMT, both including or excluding participants receiving INSTI + NNRTI. Similar results were observed for the continuous cIMT increase through adjusted linear mixed models. Propensity score matching showed no significant differences in the 2 year cIMT change between treatment groups [0.049 mm (-0.031-0.103) in the INSTI group versus 0.047 mm (-0.023-0.115) in the NNRTI group; P = 0.647]. cIMT progression was associated with traditional cardiovascular risk factors. INSTI-based regimens are not associated with increased progression of subclinical atherosclerosis when compared to NNRTI.

A retrospective study on the prognosis of endoscopic surgery for 385 early glottic cancer patients

Objective: To investigate the prognosis and influencing factors of endoscopic surgery for early glottic carcinoma. Methods: In this retrospective study, we applied the Cox proportional hazards regression model and the random survival forest model to analyze the clinical characteristics of 385 patients [362 males, 23 females, age ranging from 33 to 91 years (62.0±9.6)] who visited the Sixth Medical Center of the General Hospital of the People's Liberation Army from January 2009, to December 2022 and diagnosed with early glottic carcinoma, encompassing variables such as age, gender, T stage, surgical approach, pathological typing, etc. The primary evaluation indicators were overall survival(OS) and disease-free survival rates (DFS). The follow-up duration ranged from 30 to 5,557 days (with a median follow-up time of 1,596 days). Results: After a three-year follow-up, the OS rate for the 385 patients was 95.83%, while the DSF rate was 82.98%. The Cox proportional hazards regression analysis revealed age (HR=2.35, 95%CI: 1.75 to 3.15, P<0.001) and T staging (HR=1.59, 95%CI: 1.13 to 2.23, P=0.019) as predominant factors affecting the OS and DFS. The random survival forest model identified poor tumor differentiation, and high expression of P53 and Ki-67 as predictors of inferior prognosis. Conclusion: Endoscopic surgery for early glottic carcinoma yields favorable short-term OS and reduces short-term recurrence rates, with T-stage emerging as a pivotal factor influencing recurrence. Tumors with poor differentiation and elevated expression of P53 may be indicative of an increased risk of recurrence.

Adherence to lifelines diet is associated with lower lung cancer risk in 98,459 participants aged 55 years and above: a large prospective cohort study

BackgroundLifelines Diet Score (LLDS) was developed based on the 2015 Dutch Dietary Guidelines and current international scientific evidence. As a dietary quality assessment tool, the LLDS aims to evaluate the association between the Lifeline diet and the risk of chronic diseases. However, the evidence linking LLDS to lung cancer risk is currently limited.ObjectiveOur objective was to explore whether adherence to the LLDS is associated with reduced incidence and mortality of lung cancer, including its major histological subtypes: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC).MethodsData for this research were sourced from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Trial. The LLDS for each participant was calculated based on responses to the dietary history questionnaire (DHQ), and subsequently analyzed after being categorized into quintiles. The Cox proportional hazards regression model was utilized to compute the hazard ratios (HRs) and 95% confidence intervals (CIs) for both the incidence and mortality of lung cancer, SCLC and NSCLC. Additionally, stratified analyses were conducted to ascertain possible effect modifiers, and several sensitivity analyses were performed to evaluate the robustness of the findings.ResultsDuring the mean follow-up periods of 8.8 years for incidence and 15.1 years for mortality, we identified 1,642 new cases and 1,172 related deaths from lung cancer. Participants in the highest quartiles of LLDS compared to those in the lowest exhibited a reduced incidence (HRQ4:Q1 = 0.80, 95% CI = 0.68–0.94, P for trend = 0.003) and mortality (HRQ4:Q1 = 0.81, 95%CI = 0.67–0.98, P for trend = 0.009) of lung cancer. Furthermore, this negative association remained for SCLC incidence (HRQ4:Q1 = 0.55, 95% CI = 0.35–0.87, P for trend = 0.002) and mortality (HRQ4:Q1 = 0.42, 95% CI = 0.25–0.70, P for trend &amp;lt;0.001). The association between LLDS and the incidence and mortality of lung cancer is not influenced by pre-defined potential effect modifiers (all Pinteraction &amp;gt; 0.05). The sensitivity analyses substantiated the robustness of the results.ConclusionIn conclusion, our research indicates that among 98,459 U.S. adults aged 55 and older, adherence to the LLDS is linked to a diminished incidence and mortality of lung cancer.