Long-term Cardiovascular Risk Research Articles

Sex-specific Associations between Left Ventricular Remodeling at MRI and Long-term Cardiovascular Risk.

Background Left ventricular mass (LVM) is an established marker of cardiovascular risk; however, long-term follow-up studies in individuals with low to intermediate risk are lacking. Purpose To assess the sex-specific association of LVM measured with cardiac MRI with cardiovascular outcomes in those with a less than 20% 10-year risk of cardiovascular disease (CVD). Materials and Methods A total of 1528 volunteers older than 40 years of age with no history of CVD, a 10-year risk of CVD of less than 20%, and a B-type natriuretic peptide level greater than their sex-specific median underwent cardiac MRI between June 2008 and February 2013 as part of the Tayside Screening for Cardiac Events, or TASCFORCE, prospective study. LVM was indexed to body surface area, and the LVM-to-volume ratio was calculated. Follow-up for cardiovascular events was performed using national electronic health records. Cox proportional hazard models and Kaplan-Meier curves were applied to assess the impact of LVM. Results A total of 1495 participants (mean age, 54.5 years ± 8.3 [SD]; 925 female, 570 male) completed cardiac MRI, with a median follow-up of 10 years (IQR, 3 years). In female participants, LVM was associated with age, blood pressure, smoking status, and cholesterol level, while in male participants, LVM was associated with age and blood pressure. In female participants, the LVM-to-volume ratio was associated with cardiovascular events (hazard ratio [HR], 2.3 [95% CI: 1.1, 4.9] for the highest quartile vs the lowest quartile), while the LVM was not. In male participants, the LVM was associated with cardiovascular events (HR, 3.2 [95% CI: 1.5,7.0] for the highest quartile vs the lowest quartile), while the LVM-to-volume ratio was not. Conclusion In those with low to intermediate risk without established CVD, different remodeling patterns predict cardiovascular events, with increased LVM predictive in male participants, while LVM-to-volume ratio is predictive in female participants. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Garot and Duhamel in this issue.

Interpretable machine learning model for predicting long-term cardiovascular mortality risk in chronic kidney disease patients using SHAP explainers

Abstract Background Patients with chronic kidney disease (CKD) exhibited a pronounced burden of cardiac mortality. However, early prediction of cardiovascular mortality risk in CKD patients remains an unmet medical need. Purpose This study aimed to evaluate the performance of machine learning (ML) algorithms and identify the most influential factors in predicting long-term cardiac mortality among CKD patients. Methods Six ML models were developed, with the most effective one chosen for predicting and categorising patients into high-risk and low-risk groups based on the maximal Youden’s index. Differences in survival rates were assessed using the log-rank test on Kaplan-Meier curves. Cox regression analysis was employed to investigate the relationship between ML-predicted risk scores and mortality. Furthermore, the SHapley Additive exPlanations (SHAP) method was implemented to provide personalised explanations for model decisions. Results The auto-encoder (AE) model achieved the highest AUC of 0.94, with a sensitivity of 80.95% and specificity of 96.34%. Compared to individuals in low-risk group, those in high-risk group exhibited a significantly elevated risk of cardiovascular mortality (adjusted hazard ratio [HR]: 48.24; P <0.001). According to the SHAP model, age, C-reactive protein, blood urea nitrogen and hypertension were identified as the four most influential factors in the AE model. Conclusions Our study successfully developed an AE machine learning model for predicting 10-year cardiovascular mortality among CKD patients. The combination of ML model and SHAP aids doctors in understanding key features in the model, improving their insight into decision-making related to disease severity assessment, thus facilitating early preventive strategies in clinical practice.

Prognostic value of myocardial redox signalling: a machine learning multi-omics approach

Abstract Background Oxidative stress has been proposed to be implicated in cardiovascular pathology. Studies have linked myocardial oxidative stress with the development of atrial fibrillation, but its role in the prediction of long-term outcomes and mortality is yet to be elucidated. Purpose To apply discovery network transcriptomics and genomics to atrial tissue (AT) obtained from patients undergoing cardiac surgery, to phenotype myocardial redox-state and identify potential therapeutic targets. Methods We included 1,032 patients undergoing cardiac surgery. Arm 1 included 258 patients in whom atrial tissue (right atrial appendage) was used for ex-vivo quantification of NOX-derived superoxide by lucigenin-enhanced chemiluminescence. Arm 2 included 414 patients in whom exploratory, unsupervised gene network analysis in human atrial tissue RNA sequencing data was performed to identify atrial tissue redox-sensitive signatures (blue signature). Arm 3 included 881 patients genotyped with the genome-wide SNP array UK Biobank Axiom Array and used for machine learning construction of GenRedOx, a SNP model built to predict the blue transcriptomic signature. Associations with future incidence of major adverse myocardial events (MAME: cardiovascular death and/or heart failure) was assessed across all arms using cox regression models (adjusted for age, sex, hypertension, dyslipidaemia, diabetes mellitus, body mass index, and plasma TNFa). Results Over a median follow-up of 5.27 years [IQR: 4.29-6.83] high atrial tissue (AT) NOX-derived superoxide was independently associated with MAME risk (Adj. HR[95%CI]: 11.7 [2.18 , 62.82], p=0.004, a). Unsupervised transcriptomic analysis in Arm 2 revealed 15 coexpressed gene ‘modules’ or 'signatures' (b). The blue signature was significantly associated with AT superoxide production with "immune response-regulating and activating signalling" being amongst the top enriched pathways. Patients with high eigengene values for the blue signature showed a 5.5-fold higher adjusted risk of MAME (c). In Arm 3, extreme gradient boosting of SNP data, trained using the blue transcriptomic signature as ground truth, revealed GenRedOx (d), a genomic artificial intelligence score, which was found to be prognostic of MAME in the validation stage (e). Homozygosity for the minor allele of SNP rs723897 in the Chemokine-Like Factor Super Family 7 (CMTM7) gene had the highest gain in the model. Conclusion We present for the first time two novel human myocardial transcriptomic and genomic signatures that reflect changes in redox state and identify long-term cardiovascular risk. Targeting pathways in the myocardium related with immune response signalling may lead to the development of novel therapeutics in cardiovascular disease.

Post-operative atrial fibrillation during cardiac rehabilitation: incidence and long-term prognostic value

Abstract Background Postoperative atrial fibrillation (POAF) represents a common complication after cardiac surgery and is associated with longer in-hospital stay and increased in-hospital death and stroke, but its long-term prognostic value, during cardiac rehabilitation (CR), remains not well understood. Purpose The study aimed to assess the incidence and long-term prognostic values of different types of POAF in a cohort of consecutive patients who undergo CR after cardiac surgery. Methods A consecutive registry of patients admitted to our CR after cardiac surgery represents the present study. POAF was defined as any episode of atrial fibrillation occurring in the post-operative period from post-intensive care unit to hospital discharge after CR; moreover, POAF types were classified as Paroxysmal POAF (early and late) and persistent (early and late). Long-term hard end-points were: cardiovascular (CV) mortality and major adverse cardiovascular and cerebrovascular events (MACCEs defined as a composite of cardiovascular death, heart failure hospitalization, non-fatal myocardial infarction, and stroke). Results A total of 2.020 patients were included, mean age was 67 years and male gender was prevalent (71%). CR post-coronary artery bypass graft (CABG) was the indication of CR in 53% of patients, cardiac valve surgery in 35%, while 11% underwent CR after CABG plus valve surgery. All patients were followed for a mean of 50 months. POAF was found in 392 patients (19.4%) divided into 36% paroxysmal POAF and 64% persistent POAF, while 7.7% had permanent atrial fibrillation (figure 1A). Overall POAF was associated with higher rates of CV death (SR 5.0% vs POAF 7.2% vs pAF 16.5%; p<0.001) and MACCEs (SR 12.4% vs POAF 19.6% vs pAF 25.2%; p<0.001 – figure 1B). By analyzing separately paroxysmal, persistent, early, and late POAF, interestingly only late POAF (both persistent or paroxysmal) was associated with a higher long-term CV risk, in particular, both late persistent and late paroxysmal were associated with a higher risk of MACCEs (late persistent: OR 1.65, p=0.004 / late paroxysmal: OR 1.98, p=0.002 – figure 1C), mainly driven by a higher rate of heart failure hospitalization. Interestingly late paroxysmal POAF showed the worst outcomes among all classified POAF (figure 1D). Conclusions POAF after cardiac surgery is associated with long-term adverse outcomes, but not all POAF have the same prognostic value. Late, rather than early, POAF (whether paroxysmal or persistent) is associated with a poor long-term prognosis after cardiac rehabilitation.Figure 1

Postpartum Management of Hypertensive Disorders of Pregnancy in Six Large U.S. Hospital Systems: Descriptive Review and Identification of Clinical and Research Gaps.

Hypertensive disorders of pregnancy (HDPs) are a key contributor to maternal morbidity and mortality. Several gaps in knowledge remain regarding best practices in the postpartum management of HDPs. In this review, we describe postpartum HDPs management among six large academic U.S. hospital systems: Medical College of Wisconsin, University of Pittsburgh, University of Wisconsin-Madison, Northwestern University, University of Minnesota, and Boston Medical Center. We identified that all six health systems discharge patients with HDPs diagnosed with a blood pressure (BP) cuff and use the same two antihypertensive medications, nifedipine and labetalol, as first- and second-line treatment of HDPs. Northwestern University routinely adds oral furosemide for 5 days for patients with BP that exceeds 150/100 mm Hg. Most hospital systems administer magnesium sulfate routinely when readmission for HDPs occurs. In contrast, there was variation in BP threshold for antihypertensive treatment initiation, use of remote BP monitoring program, use of a transition clinic, delivery or lack of education on long-term cardiovascular disease risk, and BP management through the first 6 weeks postpartum and beyond. Based on the clinical review, we identified clinical gaps and formulated considerations for research priorities in the field of postpartum HDPs management. KEY POINTS: · Several gaps in knowledge remain regarding best practices in postpartum management of HDPs.. · There is a variation in the BP threshold for antihypertensive treatment initiation.. · Data are lacking on the reduction in severe maternal morbidity (SMM) and racial disparities in SMM with remote monitoring..

6618 Risks for Cardiovascular Comorbidities Associated with Desiccated Thyroid Extract Administration

Abstract Disclosure: S.C. De La Torre: None. C. Godar: None. K. Flynn: None. A.A. Patel: None. D. Maxwell: None. M.K. Shakir: None. T.D. Hoang: None. Introduction: Levothyroxine (LT4), synthetic thyroid hormone (T4), is considered the standard of care for the management of hypothyroidism based on the current American Thyroid Association (ATA) guidelines. However, there is a small subset of patients demonstrating symptomatic improvement with desiccated thyroid extract (DTE), which is composed of desiccated porcine thyroid containing T4 and triiodothyronine (T3). Limited data or studies are available exploring long-term cardiovascular effects associated with DTE use. In this retrospective review, we aim to identify possible cardiovascular comorbidities associated with DTE use. Methods: The charts of 77 patients at a tertiary hospital center (64 females and 13 males) over the age of 18 who were prescribed DTE were reviewed. Data collected include duration of treatment, dose of treatment, pre-treatment and current weight, blood pressure (BP), TSH, free T4, and total T3 levels. New cardiovascular and other events following initiation of treatment (hypertension, coronary artery disease (CAD), myocardial infarction (MI), stroke, transient ischemic attack (TIA), atrial fibrillation, type 2 diabetes, fractures) were also obtained. Averages, medians, and totals of patient data were used for analysis. Results: Average patient age was 54 years, average duration of therapy was 77.5 months, and median DTE dose was 75 milligrams per day. Review of chart documentation from DTE initiation compared to current values identified a 2.5% increase in weight, 3.6% increase in systolic BP, 0.8% decrease in diastolic BP, 60.9% decrease in TSH, 5.2% decrease in free T4, and 14.4% increase in total T3. 19.5% patients (15 total, 80% of which were female) had recorded new cardiovascular events at any time following initiation of therapy. 15 patients developed HTN, 5 developed CAD, 2 developed atrial fibrillation, 5 developed type 2 diabetes, 5 new fractures, 0 MI, 0 stroke, and 0 TIA. Conclusion: These results demonstrate new cardiovascular events in our study population following the initiation of DTE, but it is unclear whether these events were directly associated with DTE use versus other factors based on our available data. Limitations of our study include small study size, uneven gender distribution, and data significance would be improved with comparison to a control group. Additional studies are needed to further evaluate long-term cardiovascular risk factors associated with DTE use. Presentation: 6/2/2024

Maternal vascular indices and hemodynamic parameters at 36 weeks' gestation in gestational and pre-existing diabetes mellitus.

To compare maternal vascular indices and hemodynamic parameters at 35-37 weeks' gestation in pregnancies complicated by gestational diabetes mellitus (GDM), those with pre-existing diabetes mellitus (DM) and those without GDM or pre-existing DM. This was a prospective observational study in women with a singleton pregnancy attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. The visit included recording of maternal demographic characteristics and medical history, and measurement of vascular indices and hemodynamic parameters using a non-invasive operator-independent device. These included carotid-to-femoral pulse-wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressure, total peripheral resistance and heart rate. The values in the GDM and pre-existing DM groups were compared to those in the unaffected group. We examined 6746 women, of whom 396 were excluded because they had chronic hypertension or developed pre-eclampsia or gestational hypertension. The study population of 6350 pregnancies contained 99 (1.6%) with pre-existing Type-I or Type-II DM and 617 (9.7%) that developed GDM, including 261 (42.3%) that were treated with diet alone, 239 (38.7%) treated with metformin alone and 117 (19.0%) treated with insulin with or without metformin. Among women with GDM and those with pre-existing DM, compared to those without GDM or pre-existing DM, there was a higher median cardiac output and heart rate, central systolic and diastolic blood pressure and pulse-wave velocity, but there was no significant difference in stroke volume and total peripheral resistance. There were no significant differences within the GDM group according to treatment type, except for higher heart rate in women treated with metformin alone compared to the group treated with diet alone. Women with GDM and those with pre-existing DM have evidence of early vascular disease in the third trimester, and this may contribute to their increased long-term cardiovascular risk. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Atherosclerosis, cancer and immune checkpoint inhibitors

Immunotherapy has revolutionized the treatment of various cancers leading to a clear survival benefit with cured or long-surviving patients. Atherosclerosis and cancer share risk factors and molecular mechanisms and have as their common thread a state of chronic inflammation linked to a deregulation of the immune system. A growing body of evidence is accumulating on the potential worsening effect of immune checkpoint inhibitors on atherosclerosis, with subsequent worsening of patients' long-term cardiovascular risk. The molecular pathways implicated in the growth and deregulation of atherosclerotic plaques seem to be the same (CTLA-4, PD-1, PD-L1) as those on which the anti-tumor effect is exerted. Owing to the increasing number of cancer patients treated with immunotherapy and the improved survival with the possibility of prolonged disease control, it is necessary to know the potential increase in cardiovascular risk for atherosclerosis-related events and to establish all prevention measures to reduce it.

Dynamic Perioperative Platelet Activity and Cardiovascular Events in Peripheral Artery Disease

ObjectivePatients with peripheral artery disease (PAD) undergo lower extremity revascularization (LER) for symptomatic relief or limb salvage. Despite LER, patients remain at increased risk of platelet-mediated complications, such as major adverse cardiac and limb events (MACLE). Platelet activity is associated with cardiovascular events; yet little is known about the dynamic nature of platelet activity over time. We therefore investigated the change in platelet activity over time and its association with long-term cardiovascular risk. MethodsPatients with PAD undergoing LER were enrolled into the multicenter, prospective Platelet Activity and Cardiovascular Events (PACE) study. Platelet aggregation was assessed by light transmission aggregometry (LTA) to submaximal epinephrine (0.4μ M) immediately prior to LER, and on post-operative day 1 or 2 (POD1) and 30 (POD30). A hyperreactive platelet phenotype was defined as >60% aggregation. Patients were followed longitudinally for MACLE, defined as the composite of death, myocardial infarction, stroke, major lower extremity amputation, or acute limb ischemia leading to reintervention. ResultsAmong 287 patients undergoing LER, mean age was 70 ± 11 years, 33% were female, 61% were white, and 89% were on baseline antiplatelet therapy. Platelet aggregation to submaximal epinephrine induced a bimodal response; 15.5%, 16.8%, and 16.4% of patients demonstrated a hyperreactive platelet phenotype at baseline, POD1, and POD30, respectively. Platelet aggregation increased by 18.5% (P=0.001) from baseline to POD1, which subsequently returned to baseline at POD30. After a median follow-up of 19 months, MACLE occurred in 165 (57%) patients. After adjustment for demographics, clinical risk factors, procedure type, and antiplatelet therapy, platelet hyperreactivity at POD1 was associated with a significant hazard of long-term MACLE (aHR 4.61, 95% CI 2.08-10.20, P<0.001). ConclusionAmong patients with severe PAD, platelet activity increases following LER. Platelet hyperreactivity to submaximal epinephrine on POD1 is associated with long-term MACLE. Platelet activity following LER may represent a modifiable biomarker associated with excess cardiovascular risk.

Prognostic value of the monocyte-to-high-density lipoprotein-cholesterol ratio in ACS patients: A systematic review and meta-analysis.

Globally, diseases of the cardiovascular system stand as the principal contributors to mortality and are anticipated to show an upward trajectory. The occurrence of Acute Coronary Syndrome (ACS) has been linked to underlying inflammatory processes. The monocyte-to-high-density lipoprotein-cholesterol (MHR) ratio has garnered significant attention as a prognostic biomarker, encapsulating the synergistic roles of inflammation and lipid metabolism in the pathophysiology of cardiovascular diseases, including ACS. This meta-analysis examines the prognostic MHR ratio in ACS patients. We systematically searched PubMed, Embase, Scopus, Web of Science, and the Cochrane Library databases to identify the relevant meta-analyses up to February 26, 2024. The findings were aggregated into risk ratios with 95% confidence intervals. Eleven studies, with 7421 patients, were included. Low MHR levels compared to high MHR levels were associated with statistically significantly lower in-hospital mortality (0.9% vs. 5.5%; respectively; p<0.001), 3-month mortality (4.4% vs. 11.2%; p = 0.02), 6-month follow-up mortality (4.0% vs. 10.2%; p = 0.03), 1-year mortality (4.2%, vs. 10.2%; p<0.001), as well as long-term follow-up mortality (7.5% vs. 13.7%; p<0.001). MHR has both good predictive properties for mortality and MACE (short- and long-term). Data indicate that MHR may improve in-hospital and long-term cardiovascular risk prediction. It may, therefore, be an effective tool for risk re-estimation and the selection of patients for whom intensive lipid-lowering treatment may be particularly useful.

Is the KOS-Zawał coordinated care program effective in reducing long-term cardiovascular risk in coronary artery disease patients in Poland? Insights from analysis of statin persistence in a nationwide cohort.

Is the KOS-Zawał coordinated care program effective in reducing long-term cardiovascular risk in coronary artery disease patients in Poland? Insights from analysis of statin persistence in a nationwide cohort.

RNA-Seq analysis of human heart tissue reveals SARS-CoV-2 infection and inappropriate activation of the TNF-NF-κB pathway in cardiomyocytes

The negative impact of SARS-CoV-2 virus infection on cardiovascular disease (CVD) patients is well established. This research article explores the cellular pathways involved in underlying heart diseases after infection. The systemic inflammatory response to SARS-CoV-2 infection likely exacerbates this increased cardiovascular risk; however, whether the virus directly infects cardiomyocytes remains unknown due to limited multi-omics data. While public transcriptome data exists for COVID-19 infection in different cell types (including cardiomyocytes), infection times vary between studies. We used available RNA-seq data from human heart tissue to delineate SARS-CoV-2 infection and heart failure aetiology specific gene expression signatures. A total of fifty-four samples from four studies were analysed. Our aim was to investigate specific transcriptome changes occurring in cardiac tissue with SARS-CoV-2 infection compared to non-infected controls. Our data establish that SARS-CoV-2 infects cardiomyocytes by the TNF-NF-κB pathway, potentially triggering acute cardiovascular complications and increasing the long-term cardiovascular risk in COVID-19 patients.

Association between methylphenidate use and long-term cardiovascular risk in paediatric patients with attention deficit and hyperactivity disorder

BackgroundThere have been concerns about the potential cardiovascular (CV) adverse effects associated with methylphenidate (MTH) use. However, only limited evidence exists on the long-term safety of MTH.ObjectiveTo evaluate whether MTH...

Endometriosis and Long-Term Cardiovascular Risk: A Nationwide Danish study.

Endometriosis, a systemic gynecological disease affecting 10% of women in reproductive age, shares pathophysiological characteristics with cardiovascular disease. However, data on the relationship between endometriosis and cardiovascular outcomes are scarce, prompting this study to address the knowledge-gap. Using Danish nationwide registries, women diagnosed with endometriosis (1977-2021) were identified and matched with controls in a 1:4 ratio based on year of birth. The primary outcome was a composite of acute myocardial infarction and ischemic stroke. The secondary outcomes were arrhythmias, heart failure, and mortality. In total, 60,508 women with endometriosis and 242,032 matched controls were included (median age 37.3 years). Women with endometriosis were more comorbid and used more medications than controls. The incidence rates of the composite outcomes were 3.2 (95% confidence interval [CI] 3.2-3.3) and 2.7 (95% CI 2.7-2.8) per 1000 person-years among women with and without endometriosis, respectively. Women with endometriosis had a significantly higher associated rate of the composite outcome compared with controls (unadjusted hazard ratio [HR] 1.18 [95% CI 1.14-1.23], adjusted HR 1.15 [95% CI 1.11-1.20]). Likewise, women with endometriosis were also at significantly increased associated risk of arrhythmias (unadjusted HR 1.24 [95% CI 1.20-1.28], adjusted HR 1.21 [95% CI 1.17-1.25]) and heart failure (unadjusted HR 1.16 [95% CI 1.09-1.22], adjusted HR 1.11 [95% CI 1.05-1.18]) but at decreased risk of mortality (unadjusted HR 0.95 [95% CI 0.92-0.97], adjusted HR 0.93 [95% CI 0.91-0.96]). Women with endometriosis have a higher associated long-term risk of cardiovascular outcomes compared with controls. Despite subtle absolute risk-differences, the high prevalence of endometriosis underscores the importance of these findings.

Abstract P190: Blood pressure monitoring and knowledge in the first year after a hypertensive disorder of pregnancy

Introduction: In the first year postpartum, hypertension (HTN) is a leading cause of morbidity and mortality, particularly for those with hypertensive disorders of pregnancy (HDP). Timely recognition of HTN is key to reducing short- and long-term cardiovascular risk among birthing people. Therefore, we assessed knowledge of when to seek medical attention for blood pressure (BP) elevations and rates of BP measurement in the first year postpartum among those with and without HDP. Methods: This was a secondary analysis of primiparas who participated in a randomized trial of prenatal counseling to improve postpartum health. We included 405 participants who self-reported information on postpartum BP assessment. We calculated (1) the proportion of participants who stated they would contact a clinician for a systolic BP above 140 and a diastolic BP above 90 at 3-months postpartum and (2) the frequency and location of BP checks reported from 3-12 months postpartum among those with and without HDP. Subgroup analyses compared BP knowledge by sociodemographic and health-related factors. Results: Participants were 32 +/-5 years, 16% reported a HDP, 60% identified as White, 75% had private insurance, and 84% had ≥ college education. For systolic BP, 44.6% with HDP and 23.5% without HDP identified a BP of 140 as the threshold above which they would contact a clinician (p&lt;0.01); for diastolic BP, 52.4% with HDP and 28.5% without identified a BP threshold of 90 (p&lt;0.01).From 3-12 months postpartum, 83.1% with HDP and 59.4% without HDP had a BP check (p &lt; 0.01); 41.6% with HDP and 9.7 % without HDP checked their BP at home (p&lt;0.01). Home monitoring was not associated with awareness of when to contact a physician for hypertension among those with HDP (TABLE). BP awareness was higher among people who had private health insurance, ≥ college education and were non-smokers. Conclusions: Efforts are needed to improve postpartum BP assessment, self-monitoring, and awareness of when to seek medical attention for HTN, among birthing people with and without HDP.

Abstract P135: Evaluating the Impact of Cumulative Blood Pressure and Metabolic Indicators on Long-Term Cardiovascular Risk: Insights from a 9-year Nationwide Prospective Cohort Study

Background: Cardiovascular diseases (CVD) are a global health challenge, particularly for older adults. Blood pressure and the Triglyceride-Glucose (TyG) index, an insulin resistance indicator, are key predictors of cardiometabolic risks. Methods: Using data from the China Health and Retirement Longitudinal Study (CHARLS), this study followed participants without baseline CVD over 9 years. We stratified subjects by cumulative TyG and TyG-BMI indices, applying Cox proportional hazards adjusted by age and gender, and restricted cubic spline regression for CVD risk evaluation. Results: From 11,847 participants, 4,751 were analyzed, mainly females (55.25%), with a median age of 57. BMI, TyG, and TyG-BMI indices increased significantly (23.16 to 23.51 for BMI; 8.59 to 8.62 for TyG, 199.14 to 204.22 for TyG-BMI) over 4 years. Participants were categorized based on cumulative TyG and TyG-BMI medians at 25.84 and 606.43, respectively. In the lower TyG group, each SBP unit increment raised CVD risk by 0.5% at 4 years (HR = 1.005, 95% CI 1.003–1.007, p&lt;0.001) and 9 years (HR = 1.005, 95% CI 1.004–1.006, p&lt;0.001). Each 10-unit rise in cumulative DBP corresponded to an 8-9% higher CVD risk at the 4 and 9-year follow-ups. In the higher TyG group, SBP increases were significantly associated with CVD risk changes. Each 10-unit DBP rise corresponded to a non-significant 2% risk elevation at 4 years, but a significant 3% risk increase at 9 years (HR = 1.003, 95% CI 1.000–1.005, p=0.023). For those with a TyG-BMI below 606.43, minor SBP increases significantly impacted CVD risk at both 4 and 9 years. Meanwhile, each 10-unit DBP increment resulted in a 6-8% risk increase, which grew over time. Above a TyG-BMI of 606.43, SBP changes resulted in a notable 2% risk rise by 9 years, and 10-unit DBP increases resulted in a 2-3% risk rise by 9 years. Restricted cubic spline regression showed the 4 and 9-year CVD risk increased with each rise in cumulative SBP and DBP when cumulative TyG was &lt;25.84 or cumulative TyG-BMI &lt;606.43, and DBP had a more profound impact. In contrast, trends were unclear when cumulative TyG ≥25.84 or cumulative TyG-BMI ≥606.43. Conclusion: Cumulative SBP and DBP increases are linked to higher CVD risks, especially in individuals with lower cumulative TyG or TyG-BMI indices. DBP effects were more substantial, particularly noticeable over 9 years. This study underscores the nuanced impacts of blood pressure and metabolic indicators on long-term cardiovascular health.

Insulin-based or non-insulin-based insulin resistance indicators and risk of long-term cardiovascular and all-cause mortality in the general population: A 25-year cohort study

ObjectiveAlthough insulin resistance (IR) has been recognized to be a causal component in various diseases, current information on the relationship between IR and long-term mortality in the general population is limited and conclusions varied among different IR indicators and different populations. We aimed to assess associations between different measurements of IR with long-term all-cause mortality and cardiovascular mortality risk for the general population. Research design and methodsWe included 13,909 individuals from the Third National Health and Nutrition Examination Survey. Mortality was identified via National Death Index information until December 31, 2019. IR was measured using fasting insulin, homeostasis model assessment of IR (HOMA-IR), homeostasis model assessment of β-cell function, quantitative insulin sensitivity check index (QUICKI), insulin-to-glucose ratio (IGR), triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), and hypertriglyceridemic-waist phenotype. ResultsDuring median 25-year follow-up, 5,306 all-cause mortality events occurred. After multivariate adjustment, variables significantly associated with elevated all-cause mortality risk were (hazard ratio [95 % confidence interval]): higher insulin (1.07 [1.02;1.13]); HOMA-IR (1.08 [1.03;1.13]); IGR (1.05 [1.00;1.11]); TyG (1.07 [1.00;1.14]); TyG-BMI (1.24 [1.02;1.51]); lower QUICKI (0.91 [0.86–0.96]). After stratification by diabetes status, higher insulin, HOMA-IR, TyG-BMI and lower QUICKI were significantly associated with increased risk of all-cause mortality in both diabetes and non-diabetes populations (all P for interaction > 0.05). Higher TyG (adjusted HR 1.17 [1.09;1.26], P for interaction = 0.018) and hypertriglyceridemic-waist phenotype (adjusted HR 1.26 [1.08;1.46], P for interaction = 0.047) were significantly associated with increased risk of all-cause mortality in patients with diabetes, however, these associations could not be seen in people without diabetes. Similar results were observed between the above-mentioned IR indicators and cardiovascular death. ConclusionsFasting insulin, HOMA-IR, TyG-BMI, and QUICKI may indicate mortality risk in diabetes and non-diabetes populations, with TyG and the hypertriglyceridemic-waist phenotype showing particular relevance for individuals with diabetes. Further studies are needed to validate these findings and determine their broader applicability.

Association of baseline serum sodium with long-term outcomes in newly diagnosed coronary heart disease patients without heart failure: a prospective cohort study

Sodium is crucial for maintaining cardiovascular health, especially in relation to heart failure. The impact of baseline serum sodium concentrations on the outcomes of newly diagnosed coronary heart disease (CHD) without heart failure remains unclear. This prospective cohort study included 681 patients who were newly diagnosed with CHD. Cox proportional hazards models and restricted cubic spline (RCS) analysis were used to assess the relationship between serum sodium concentrations and major adverse cardiovascular events. The improvement in traditional prediction models by the addition of serum sodium concentrations was assessed using changes in the C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). During a median follow-up of 51.04 months (IQR: 40.88–53.80 months), 131 events were recorded. Multivariate Cox proportional hazards models showed that the L2 group (136–138.9 mmol/L) had the highest MACE risk. Compared to L2, the hazard ratios (HRs) and 95% confidence intervals (CIs) for the L1 (130–135.9 mmol/L), L3 (139–140.9 mmol/L), L4 (141–142.9 mmol/L), and L5 (143–147.0 mmol/L) groups were 0.31 (0.14–0.70, P = 0.005), 0.48 (030–0.78, P = 0.003), 0.56 (0.34–0.92, P = 0.022), and 0.37 (0.22–0.64, P < 0.001), respectively. Including serum sodium concentrations in the prediction model significantly improved the C-statistic from 0.647 to 0.679 (P = 0.022), with an NRI of 0.338 (P < 0.001) and an IDI of 0.026 (P < 0.001). RCS analysis showed a nonlinear relationship: within the 130–138 mmol/L sodium range, MACE risk gradually increased with higher sodium levels (HR 1.39, 95% CI 1.09–1.76, P = 0.008); whereas within the 138–147 mmol/L range, the risk gradually decreased (HR 0.88, 95% CI 0.80–0.98, P = 0.014). Baseline serum sodium concentrations are significantly associated with long-term cardiovascular risk in newly diagnosed CHD patients, showing an inverted U-shaped relationship, whereas low serum sodium may be specifically linked to higher risks of death and nonfatal myocardial infarction. Further research is needed to explore the impact of long-term changes in serum sodium concentrations on disease prognosis.

Biological use influences the impact of inflammation on risk of major adverse cardiovascular events in rheumatoid arthritis

ObjectivesChronic inflammation promotes cardiovascular risk in rheumatoid arthritis (RA). Biological disease-modifying antirheumatic drugs (bDMARDs) improve disease activity and cardiovascular disease outcomes. We explored whether bDMARDs influence the impact of disease...

Effects of combined morbid insomnia and sleep apnea on long-term cardiovascular risk and all-cause mortality in elderly patients: a prospective cohort study

PurposeIt is reported that insomnia and obstructive sleep apnea (OSA) increase the incidence of adverse cardiovascular events. The aim of this study was to analyze the risk of cardiovascular disease and mortality in elderly patients with comorbid insomnia and obstructive sleep apnea (COMISA).MethodsWe included 868 elderly patients with OSA who underwent sleep monitoring at a multicenter sleep room from January 2015 to October 2017. We collected demographic data, clinical features, medical history, sleep parameters, and laboratory findings. Cox proportional hazards analysis was used to identify the relationship between COMISA and adverse cardiovascular events and all-cause mortality.ResultsThere were 181 elderly patients with COMISA. The median follow-up was 43 months, during which we observed major adverse cardiac events (MACE) in 90 patients. The Kaplan-Meier survival curve indicated a significant relationship between COMISA and MACE (Plog Rank < 0.001). Multivariate Cox regression analysis showed that COMISA increased the incidence of MACE (HR = 2.328, 95% CI: 1.349–4.018, P = 0.002), hospitalization for unstable angina (HR = 2.915, 95% CI: 1.397–6.081, P = 0.004), and the combination of all events (HR = 2.301, 95% CI: 1.393–3.803, P = 0.001). However, there were no significant differences in cardiovascular death, all-cause mortality, myocardial infarction, or hospitalized heart failure in patients with COMISA (P > 0.05). Subgroup analyses showed that among COMISA patients, male sex (HR = 2.800, 95% CI: 1.458-5.377, P = 0.002), age < 70 years (HR = 4.050, 95% CI: 2.022–8.115, P < 0.001), and overweight and obesity (HR = 2.482, 95% CI: 1.383-4.453, P = 0.002) were associated with a higher risk of MACE.ConclusionsOur results showed that COMISA increased the risk of MACE, unstable angina, and the compound occurrence of all events. Male, overweight or obese COMISA patients under 70 years of age have an increased risk of MACE.