bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and incidence of heart failure in patients with type 2 diabetes mellitus. Results of the prospective DIABET-IC study
Authors: Gonzalez-Manzanares R , Anguita Gamez M , Muniz Garcia J , Barrios Alonso V , Perez Perez A , Gimeno Orna J A , Rodriguez Padial L , Anguita Sanchez M
Published: October 2024

Introduction

Heart failure (HF) is one of the major health problems in our environment today. Type 2 diabetes mellitus (DM2) is an important cardiovascular risk factor and can increase the burden of HF through various mechanisms. The incidence of HF in DM2 has not been well studied.

Purpose

The aim of our study was to evaluate the prevalence and incidence of HF in patients with DM2 followed in hospital cardiology and endocrinology departments.

Methods

The DIABET-IC study is a longitudinal cohort, prospective, multicenter follow-up study that included 1,249 consecutive patients with DM2 in 2018-2019 in 30 Spanish centers in cardiology and endocrinology outpatient clinics. HF was diagnosed according to the clinical records and following the criteria of the European Society of Cardiology. The prevalence of HF at the inclusion visit was analyzed, as well as the incidence of HF (new diagnoses) during a 3-year follow-up.

Results

Mean age was 67.3±+9.9 years, with 31.7% of the patients being women. Cardiology clinics included 61.9% of patients and endocrinology clinics the remaining 38.1%. There was a previous history of coronary artery disease in 38.6%, hypertensive heart disease in 21% and atrial fibrillation in 31.9%. Cardiovascular and antidiabetic drugs prescribed at the baseline and 3-year visits are shown in figure 1. Figure 2 summarizes the results of the study. The prevalence of HF at the baseline visit was 39.2%, 490 cases (with reduced LVEF 17.3%, mildly reduced 8.1% and preserved 13.8%). After a follow-up of 1,935/100 persons-year of cases without baseline HF, 58 incident cases of HF were diagnosed, 7.6% (32 in the first year, 13 in the second and 13 in the third year of follow-up). The incidence rate was 3.01/100 person-years (95%CI: 2.30-3.92). Of these 58 cases, 23.7% were with reduced LVEF, 28.9% with slightly reduced LVEF and 47.4% preserved. The incidence was higher in patients followed by endocrinology (3.90 vs 2.90/100 persons-year; p=0.042). At the end of the 3-year follow-up, including baseline prevalence, 46.8% of all patients had HF.

Conclusions

The prevalence and incidence of HF in patients with DM2 are very high. The incidence of HF is around 3% per year, which is almost 8 times higher than the rate found in large studies in the general population. Approximately half of the new cases were HF with preserved LVEF, and the other half with LVEF < 50%. The use of new antidiabetic drugs, such as iSGLT2, which have been shown to reduce the incidence of HF, should be encouraged.
Applicability of VICTORION-1 PREVENT Criteria to the US Population
Authors: Aggarwal R , Bhatt D , Bonaca M , Deck C , Lesogor A , Patel M , Stroes E , Taub P , Windecker S
Published: October 2024

Background

VICTORION-1 PREVENT (V-1P) is an ongoing randomized clinical trial comparing inclisiran sodium 300mg every six months with placebo for primary prevention in patients with high cardiovascular (CV) risk.

Purpose

We evaluated the generalizability of V-1P trial enrollment criteria to the US population to understand the demographic and CV health characteristics of the trial target population.

Methods

We included data from the National Health and Nutrition Examination Survey (N=25,531, 2015-March 2020), a nationally representative sample of the US population. Enrollment criteria similar to V-1P were applied. Nonpregnant adults 40-79 years with low-density lipoprotein cholesterol (LDL-C) of 70-189 mg/dL were included. 10-year risk for CV disease was determined using the American Heart Association race-free 10-year PREVENT risk equations. Individuals with 10-year risk >20% or 7.5%-19.9% with two risk enhancing factors at baseline were included. Risk enhancing factors included elevated high sensitivity C-reactive protein (≥2 mg/L), inflammatory arthritis, estimated glomerular filtration rate <60 ml/min/1.73 m2, metabolic syndrome, or early family history of CV disease. Patients with history of atherosclerotic CV disease or liver disease were excluded. Estimates of demographics and health characteristics were nationally representative using survey weights.

Results

Among US adults, 21,576,506 (standard error [SE]: ±1,258,255) meet eligibility criteria for V-1P (weighted estimate). This represents 8.8% of all US adults or 15.1% of US adults 30-79 years. The V-1P eligible population had a mean age of 65.3 years (SE: ±0.5 years), and 55.0% (SE: ±2.5%) were female.

Compared with the US adult population (≥18 years), V-1P eligible population had a higher mean body mass index (32.6 ± 0.3 kg/m2 vs 29.5 ± 0.2 kg/m2) and higher rates of obesity (61.0% ± 2.1% vs 40.0% ± 1.1%) (Table). V-1P eligible population also had higher mean systolic blood pressure (133.9 ± 1.0 mmHg vs 121.7 ± 0.3 mmHg), similar mean diastolic blood pressure (72.6 ± 0.8 mmHg vs 71.8 ± 0.2 mmHg), and higher rates of hypertension (85.8% ± 2.0% vs 45.9% ± 1.1%). Mean hemoglobin A1c percent (6.3 ± 0.1 vs 5.7 ± 0.02), fasting blood sugar (127.7 ± 1.9 mg/dL vs 109.2 ± 0.6 mg/dL), and diabetes rates (39.7% ± 2.6% vs 13.1% ± 0.7%) were higher in the V-1P eligible population. Mean low-density lipoprotein cholesterol (115.8 ± 1.5 mg/dL vs 110.2 ± 0.8 mg/dL) and fasting triglycerides (137.6 ± 5.0 mg/dL vs 110.4 ± 1.7 mg/dL) were higher, while mean high-density lipoprotein cholesterol was lower (49.9 ± 0.8 mg/dL vs 54.8 ± 0.4 mg/dL). The distribution of key CV risk factors is shown in the Figure.

Conclusion

V-1P enrollment criteria apply to many patients. These patients have significant cardiometabolic risk factor burden, and effective preventive therapies could have substantial health impact.
Identifying clinical phenotype clusters for coronary artery disease: a novel approach using clustering by unsupervised machine learning
Authors: Holtrop J , Lim C E , Uijl A , Ueda P , Jernberg T , Van Der Meer M G , Kraaijeveld A O , Balder J , Hageman S H J , Visseren F L J , Dorresteijn J A N
Published: October 2024

Background

Guideline recommendations for the prevention of cardiovascular (CV) events in patients with coronary artery disease (CAD) are one-size-fits-all. Clinically identifiable phenotypes needing specific considerations might exist.

Purpose

To identify phenotypes in patients with CAD based on clinical characteristics and their relationship with the risk of new CV events and treatment benefits.

Methods

Unsupervised machine learning through latent class analysis (LCA) was performed on patients with CAD included in the UCC-SMART cohort (n = 5,888) and SWEDEHEART registry (n = 67,428), to identify patient clusters (i.e., phenotypes) based on clinical characteristics: age, sex, body-mass-index, diastolic blood pressure, history of diabetes, myocardial infarction, atrial fibrillation, polyvascular disease, current smoking, non-high density lipoprotein cholesterol, estimated glomerular filtration rate, and C-reactive protein. Number of clusters was determined using the Bayesian information criterion. Event free survival and hazard ratios (HR) for major adverse cardiovascular events (MACE) as primary endpoint, including non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, were estimated per cluster. The LCA were performed in each respective cohort and cross-validated in the other cohort to assess impact of variations in clustering variables on cluster reproducibility. In UCC-SMART, bootstrapping was performed the assess stability of the LCA model and impact on cluster assignment.

Results

In UCC-SMART four distinct phenotypes within the CAD population could be distinguished: Phenotype A (16%) of mostly males with isolated CAD, phenotype B (30%) of older patients with polyvascular disease, Phenotype C (28%) of only women with limited traditional risk factors and Phenotype D (27%) young, current smokers with a premature event (Figure 1). Cross-validation in SWEDEHEART identified roughly the same four phenotypes, i.e., phenotype A (39%) with 100% males and 3.8% polyvascular disease, phenotype B (8%) with average age of 71 years and 30% polyvascular disease, phenotype C (19%) with 100% women, and phenotype D (34%) 54 years and 25% current smokers. Notably, although age was comparable between phenotype A and C, MACE-free survival was worse for the female-only cluster. Similarly, although patients where on average 9 years younger in phenotype D when compared to phenotype A, MACE-free survival was worse (Figure 2). No significant changes in clustering models were observed in the bootstrap samples.

Conclusion

Phenotypes can be distinguished within patients with CAD. These phenotypes are related to differences in the risk of recurrent events. These findings suggest that specific guideline recommendations for these groups could be considered.Cluster interpretation in SMARTSurvival along cluster lines
Impact and determinants of depression in cardiac hospitalized patients
Authors: Gascuena R , De Blas C , Gomez Diego J , Ruesgas R , Jimenez Azzaoui B , Grande J M
Published: October 2024

Depression increases cardiovascular risk and involves worse clinical outcomes. Little attention is paid to it in hospitalized patients. We studied prevalence and determinants of depression in this group, in order to select patients for further specific management.

Methods

Consecutive patients admitted to Cardiology wards were included. Cardiovascular risk factors, clinical and psychosocial data were collected. Self perceived mental and physical health quality were assesed by 12-item Short Form survey (SF-12), and Hospital Anxiety and Depression Scale (HADS) questionnaires were administered. Statistical analysis was performed using Spearman´s correlation, Mann-Whitney and Fisher tests, and Mantel-Cox, linear and logistic regression analyses.

Results

170 consecutive patients, median age 74.5 (67.2-81.1), 59.4% male, were included. Most common pathologies were heart failure (44.7%) and coronary syndroms (28.8%).

According to HADS results, depression was probable (score >10) in 10%, and at least possible (score > 8) in 27.1%. Both increased duration of hospitalization (Median 14 vs 7 days;p=0.016 and 11 vs 7 days;p=0.005 respectively). Anxiety was present in 16.5 % for probable case and 34.1% for possible case, with no significant change in median duration of hospitalization. 22.9% of patients were under antidepressant treatment, and 24% under anxiolytics, but they were added to treatment only in 1% and 7% respectively. No other not pharmacological measure was initiated.

Self perceived mental health was diminished in probable depression (mean difference 14.9%;95%IC 9.7-20.2;p<0.001). Self perceived physical health was also lower (mean difference 6.4%;95%CI:1.1-11.8;p=0.016).

Patients with depression were a mean of 5.6 years older (95%CI 1.4-9.8;p=0.032). Less than primary education (OR 5.69 (p 0.021), and Previous hospital admission OR 3.2 (1.0-10.3;p=0.034) increased the risk of depression in univariate analysis.

By multivariate analysis, determinants of depression were anxiety (OR 22.5;95%CI 5.9-85.6;p<0.0001), need for surgery (OR 12.3;95%IC 2.1-73.2;p=0.009), need for intensive care unit surveillance (OR 4.2;95%CI 1.1-15.8;p=0.039), and age (OR 1.1;95%IC 1.0-1.2;p=0.001. AUC was 0.89;95%CI 0.81-0.96;p<0.0001.

There was no difference in civil status, gender, income level, living accompanied, number of comorbidities, cardiovascular risk factor or reason for hospital admission.

Conclusions

Depression was prevalent in our hospitalized cardiac patients,in spite of previous pharmacological treatment. It prolongs duration of stay and impacts negatively in self perceived mental and physical health. Risk is increased in older people requiring intensive care surveillance or surgery, and specially by anxiety. These patients could benefit from a preventive multifactorial approach. Attention should also be paid to patients with a previous hospitalization and low educational level.ROC curve for multivariate model
Hearts and minds: a community-based systems diagram exploring mental health following a cardiac event
Authors: Gauci S , Cartledge S , Bastawy E M , Marx W , Gordon N , Driscoll A , Redfern J , Briffa T , Gallagher R , O'neil A
Published: October 2024

Background/Introduction

Following an acute cardiac event, individuals commonly face multiple emotional and mental health challenges. For many people, this change in their mental health will resolve over time. However, one in five will go on to develop major depressive disorder. The development of major depressive disorder is a complex co-morbidity that, if left unchecked, can increase the risk of subsequent cardiac events and mortality. Systems thinking methodology offers a novel approach to investigating factors that contribute to mental health following a cardiovascular event.

Purpose

This project aims to (1) unravel the complex system influencing mental health after a cardiac event and (2) pinpoint priorities for supporting individuals' mental well-being following a cardiac event.

Methods

Group model building workshops using Deakin University’s purpose-built STICKE software were conducted over Zoom to explore the interrelationships contributing to mental health following a cardiovascular event. Twelve participants, including consumers (n = 3) and healthcare professionals (n = 9) from across Australia, engaged in two 1.5-hour workshops. Guided by the prompt "Reflect on factors influencing a person’s mental health post-cardiac event", participants worked together to construct a systems diagram. This facilitated exploration, visual mapping, and identification of factors and priority areas influencing mental health post-cardiac event. The diagram was then analysed using the theoretical domains framework.

Results

The STICKE diagram developed demonstrates the interplay of various factors impacting mental health across the cardiac healthcare journey at both patient and system levels (see Figure 1). Using the theoretical domains framework, eight domains were identified: knowledge, skills of healthcare professionals, environmental context, personal context, emotional response to event and recovery, social influences, behavioural regulation, and beliefs about individual capacity. Knowledge (including health literacy and staff training), environmental context (addressing gaps in care and navigating the system), and social influences (such as social isolation) were domains that were consistently raised in the workshop (see Figure 2). Stakeholders also identified the following key priority areas: highlighting the need for additional support for staff and intervention to increase health literacy and knowledge around mental health.

Conclusion(s)

Supporting mental health post-cardiac events is a multifaceted challenge requiring a comprehensive community-level intervention, particularly in the initial weeks post-hospitalisation. The insights gained from this study will inform the co-design of an intervention aimed at increasing health literacy and knowledge around mental health following a cardiovascular event.
Hypnotic use and the risk of cardiovascular diseases in insomnia patients
Authors: Xie Y , Zhu S , Wu S , Liu C , Shen J , Jin C , Ma H , Xiang M
Published: October 2024

Background

Insomnia, commonly treated with hypnotic agents, is an independent risk factor of cardiovascular diseases. Previous research demonstrated the detrimental effect of hypnotics on the prognosis of cardiovascular patients.

Purpose

We aimed to examine the association between hypnotic agents and cardiovascular outcomes in general individuals with insomnia.

Methods

In a propensity score matched cohort of UK Biobank (UKB) participants with insomnia, Cox proportional hazard model was used to estimate the association between regular use of hypnotic agents and predetermined cardiovascular outcomes including incident coronary heart diseases (CHD), heart failure (HF), stroke, and cardiovascular death. Inverse probability of treatment weighting and competing risk models were further performed during sensitivity analysis. Drug-target Mendelian randomization (MR) analyses were employed for further evaluation of hypnotics-related genes and cardiovascular disease association. The genome-wide association data of CHD, HF, and stroke were there large-scale genome-wide association analyses. Tissue-specified expression quantitative trait loci (eQTL) data was derived from BrainSeq phase II.

Results

During a median follow-up of 14.3 years, the matched cohort documented a total of 1,019 CHD cases, 406 HF cases, 285 stroke cases, and 197 cardiovascular deaths. No significant association was detected between Z-meds and CHD, stroke, and cardiovascular mortality. Benzodiazepine use was significantly associated with the increased risk of CHD, HF, and cardiovascular mortality (Figure 1). The inverse probability of treatment weighting and competing risk models didn’t alter the above associations. Moreover, drug-target MR analyses corroborated the safety of Z-meds in the general population regarding cardiovascular health. However, GABRG1—a drug target for benzodiazepines—was associated with heightened risks for heart failure, and ischemic stroke (Figure 2).

Conclusions

Our findings suggested the heterogeneous associations between different categories of hypnotics and incident cardiovascular events in individuals with insomnia. Z-meds are safe regarding the risk of cardiovascular outcomes in the UKB population with insomnia.Figure 1Figure 2
Sleep characteristics in relation to cardiovascular disease incidence and mortality in individuals with diabetes
Authors: Chen Z , Liu B , Hu Y , Rimm E , Huang T , Sun Q
Published: October 2024

Background/Introduction

Evidence regarding the potential health effects of sleep characteristics among individuals with type 2 diabetes (T2D) is limited.

Purpose

We aimed to examine sleep characteristics in relation to subsequent risk of cardiovascular disease (CVD), including coronary heart disease (CHD), and stroke, and all-cause and cause-specific mortality among individuals with T2D.

Methods

We prospectively followed 21,902 men and women with T2D at baseline or diagnosed during follow-up (Nurses' Health Study: 1986-2018, Health Professionals Follow-Up Study: 1986-2018). Sleep characteristics, including sleep duration, snoring, sleep apnea, and sleep quality, were repeatedly assessed using self-reported questionnaires at baseline and follow-up. Associations of sleep characteristics with CVD risk and mortality were assessed using Cox proportional hazards models with adjustments for demographic, dietary and lifestyle factors, and medical history.

Results

During 170,355 and 196,458 person-years of follow-up in participants with T2D, there were 2,486 incident CVD events and 3,922 deaths, respectively. Compared with sleeping for 7-8 h/day, the multivariable-adjusted hazard ratios (HRs) of sleeping for ≤5 h/day were 1.21 (1.02, 1.45) for CVD incidence, 1.24 (1.20, 1.51) for CHD incidence, 1.40 (1.24, 1.58) for total mortality, 1.52 (1.20, 1.92) for CVD mortality, and 1.27 (1.01, 1.61) for other non-CVD and non-cancer mortality, while the HRs of ≥10 h/day were 1.42 (1.21, 1.66) for total mortality, and 1.63 (1.20, 2.10) for other non-CVD and non-cancer mortality. Furthermore, compared with participants without habitual snoring, those with habitual snoring had a 21%, 24%, 18%, and 33% higher risk for CVD incidence, CHD incidence, CVD mortality, and total mortality, respectively. Compared with participants without diagnosed sleep apnea, those with sleep apnea had a 27%-58% higher risk for CVD incidence, CVD mortality, and total mortality. In addition, lower habitual sleep quality, including sleep difficulties and restless sleep, was associated with a substantially higher risk of CVD, CHD, or CVD mortality. No associations were observed between sleep characteristics with risk of stroke and cancer mortality in individuals with T2D.

Conclusions

Short and long sleep durations as well as habitual snoring, sleep apnea, and lower sleep quality were independently associated with higher risks of CVD incidence and mortality, particularly CVD mortality in individuals with T2D.
Is there a gender difference in the effects of cardiovascular risk factors on the anatomical localization and severity of obstruction on coronary arteries?
Authors: Keser N , Korkmaz Y , Dogan S , Torun A , Yavuz S , Babaoglu M , Seker M , Erdem A , Orhan A L
Published: October 2024

Background

Whether there is a gender difference in the effects of traditional cardiovascular risk factors(CVRF) on the anatomical localization(AL) and severity(AS) of obstruction on coronary arteries(CA) remains unclear.

Purpose

In our study, we investigated whether there is a gender difference in the relationship between CVRF and obstruction on CA .

Methods

We included 978 patients(49.9% women, mean age: 61+10.3) with stable chest pain undergoing invasive coronary angiography between 2019-2021 who were recruited from the database of our clinic. We examined the gender difference in hypertension(HT), diabetes mellitus(DM), smoking, hyperlipidemia, previous history of CAD(H.CAD) and family history of premature CAD(F.CAD) and their correlation with the AL and AS of obstruction on CA in both gender.

Results

Women were older(p<0.001) with higher rates of HT (p=0.001) and DM(p=0.026) and higher TC, LDLC and HDLC levels respectively (rs) as (p=0.001, p=0.001, p=0.001). Whereas H.CAD and smoking rates were higher in men rs as (p=0.001, p=0.009).

The incidence of critical stenosis (≥70 obstruction) & intermediate lesions (50-69%) on all CA and Syntax scores were higher in men(p<0,01).

In patients with HT, severe CAD was more prominent on circumflex (Cx)(p=0.029) and right coronary artery(RCA)(p=0.002) in women and on the proximal ( p=0.024) and mid portion of left anterior descending artery(LAD) (p=0.045) in men.

In patients with DM a statistically significant(ss) correlation was found between the presence of DM and AS in all vessels except for left main coronary artery (LMCA) in women (LAD prox:p=0.001; LAD mid:p=0.001; diagonal artery(Dg):p=0.003; Cx:p=0.001; RCA:p=0.001 ;LMCA:p>0.05). However no such correlation was observed in men(p>0.05).

In patients with H.CAD moderate/severe lesions were more common on proximal(p=0.013) and mid portions of LAD(p=0.021), on CX( p=0.006) and on RCA(p=0.016) in men and more common on the proximal portion of LAD(p=0.047), CX(p=0.014) and RCA(p=0.009) in women. For either smoking and F.CAD there was no such correlation in either gender (p>0,05). As for blood lipid levels no correlation was observed between LDLC, HDLC and triglyceride levels and AL&AS in men(p>0,05). However there was a negative, weak correlation between the HDLC levels and obstruction on LAD mid portion(r=-0.140; p=0.003); on Dg(r=-0.100; p=0.034) on CX (r=-0.154; p=0.001) and on RCA (r=-0.151; p=0.001) in women.

Conclusion

Major traditional CVRFs have a sex specific impact on AL and AS of obstruction on CA. In the era of precisıon medicine we need gender specific risk scoring systems taking these gender differences into account.
Cardiovascular risk prediction using metabolomic biomarkers and polygenic risk scores: a cohort study and modelling analyses
Authors: Ritchie S , Jiang X , Pennells L , Xu Y , Coffey C , Liu Y , Surendran P , Karthikeyan S , Lambert S , Danesh J , Butterworth A , Wood A , Kaptoge S , Di Angelantonio E , Inouye M
Published: October 2024

Background/Introduction

Metabolomic biomarker scores and polygenic risk scores (PRS) have shown promise for improving cardiovascular disease (CVD) prediction, but have not yet been evaluated in the context of current prediction models (SCORE2) and ESC recommendations for 10-year prediction of fatal and non-fatal CVD.

Purpose

To assess whether metabolomics biomarkers and PRSs can improve 10-year CVD risk prediction when added to SCORE2, and whether improvements are meaningful at ESC 2021 recommended risk thresholds for treatment consideration.

Methods

Metabolomics biomarker scores were constructed and compared to PRS and SCORE2 in 170,000 UK Biobank participants (5,096 incident CVD cases) aged 40–69 without previous CVD, diabetes, or lipid-lowering treatment. Improvement in risk discrimination when added to SCORE2 was assessed using Harrel’s C-index. Improvement in risk stratification following ESC guideline risk thresholds was assessed using categorical net reclassification. Population modelling was subsequently applied to estimate the impact on CVD prevention if applied at scale.

Results

Risk discrimination provided by SCORE2 (C-index: 0.718) was similarly improved by addition of metabolomic biomarker scores (ΔC-index: 0.011 [0.009–0.014]) and PRSs (ΔC-index 0.009; [0.007–0.012]). Addition of both metabolomic biomarker scores and PRSs to SCORE2 yielded the largest improvement risk discrimination, with ΔC-index 0.019 (0.016–0.022). Concomitant improvements in risk stratification were observed in categorical net reclassification index, with net case reclassification of 13.04% (11.67–14.41%). Modelling metabolic biomarker scores and PRSs for targeted risk-reclassification increased the number of CVD events prevented per 100,000 screened from 201 to 370 (ΔCVDprevented: 170 [158–182]) while essentially maintaining the number of statins prescribed per CVD event prevented.

Conclusions

Combining metabolomic biomarker scores and PRSs with SCORE2 moderately enhances prediction of first-onset CVD, and could have substantial population health benefit if applied at scale.
Trajectories of lipid profile during adolescence and risk of subclinical atherosclerosis in early adulthood: a two-decade population-based study
Authors: Esmaeili F , Tohidi M , Khalili D , Valizadeh M , Momeni Moghaddam A , Abdi A , Azizi F , Hadaegh F
Published: October 2024

Background/Introduction

Recent studies have shown the highest burdens of premature cardiovascular diseases (CVDs) in the Middle-eastern, and North Africa (MENA) region. The role of dyslipidemia, as a major metabolic disturbance, in the progression of subclinical atherosclerosis and subsequently premature CVDs, indicated by carotid intima-media thickness (cIMT), must not be overlooked, specifically in young adults.

Purpose

To examine the impact of early-life lipid profile trajectories in adolescence on subclinical atherosclerosis, evidenced by cIMT in adulthood.

Methods

In this trajectory analysis, with 1006 participants (472 male, mean age=14.72±3.23 years), latent class growth modeling, particularly Group-based multi-trajectory modeling (GBMTM) was used to analyze the heterogeneity in the longitudinal lipid alterations (total cholesterol [TC], triglycerides [TG], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and non-HDL-C). The trajectories were named based on direction (rising/decreasing) and slopes of the associated trends in lipid alterations (stable/ slow/ rapid). The association between lipid trajectories, and cIMT values, both as continuous and categorical variables, were evaluated using multivariate regression analysis adjusted for age, sex, body mass index, and systolic blood pressure at the baseline, as well as antihypertensive and lipid-lowering drug use, smoking, physical activity, and desired lipid parameter at the nearest survey to cIMT measurement.

Results

During a median follow-up of 17.6 years, the "Rising" trajectories of TC, TG, LDL-C, and non-HDL-C were linked to elevated cIMT values (in the fully-adjusted model beta-coefficients [βs]=0.08 [-0.01,0.14], 0.11 [0.05,0.17], 0.13 [0.05,0.21], and 0.12 [0.06,0.18], respectively). The "Rapid-Rising" trajectories of TG, LDL-C, and non-HDL-C notably amplified the risk (in the fully-adjusted model odds ratios (OR)=2.05 [1.46-2.75], 1.99 [1.35-2.92], and 2.02 [1.45-2.77], respectively). Conversely, the "Decreasing" trajectories of TC, LDL-C, and TG were associated with lower cIMT measures (βs =-0.09 [-0.16,-0.03], -0.11 [-0.17,-0.01], and -0.08 [-0.14,-0.02], respectively); also "Decreasing" trajectories of TC and LDL-C lowered the risk by at least 30% in the fully-adjusted model (ORs=0.59 [0.39-0.81] and 0.68 [0.41-1.02], respectively). While HDL-C "Rapid-Decreasing" trajectory doubled the risk of elevated cIMT (OR=1.98 [1.47-2.68]).

Conclusion

The findings showed the unfavorable trajectory alterations in all lipid parameters were significantly associated with higher cIMT values, underscoring the need for sustained efforts to monitor lipid levels from early adolescence.
Predicting atrial fibrillation within 7 years follow-up using machine learning models
Authors: Tsarapatsani K H , Biros D , Tsakanikas V , Sakellarios A , Trampisch H J , Rudolf H , Matsopoulos G K , Fotiadis D I
Published: October 2024

Background

The prevalence of atrial fibrillation (AF), the most common type of cardiac arrhythmia, has increased globally. AF is also the leading cardiac factor for several cardiovascular and cerebrovascular events. Early prediction and treatment of AF prevents major cardiovascular and cerebrovascular events.

Purpose

Our objective is to predict AF risk within 7-years follow-up using only twelve basic factors and applying machine learning (ML) models.

Methods

Data from the German epidemiological trial on ankle brachial index (getABI) were utilized in this work. GetABI includes 6,457 patients with mean age of 72.53 years. 3,985 individuals were assessed for AF of which 393 patients suffered from AF at 7-years follow-up. The feature selection was initially done manually, ending up in 45 features. The 10 best features were extracted from this dataset according to the SHAP (SHapley Additive exPlanations) values. The final features were body mass index, sensitive CRP, cholesterol, LDL-cholesterol, troponin I, NT-pro-BNP, glomerular filtration rate, ratio of triglycerides and HDL-cholesterol, gamma-GT, heart rate, including age and sex as major factors. The handling of missing values was achieved by SimpleImputer, estimating the mean values. XGBoost and Random Forest predicted AF. Logistic Regression was also used as a baseline model. The data were split into training and test set and ML models were applied for 100 iterative runs, extracting results with mean values.

Results

XGBoost was the most accurate model, predicting the AF with 71.19 % mean accuracy, 66.37 % mean sensitivity and 75.61 % mean specificity. Figure 1 depicts the performance of all models. Additionally, Receiver Operating Characteristic Curve (ROC) and Area Under Curve (AUC) for each model are presented in Figure 2. XGBoost also outperformed all the others models, achieving the highest mean AUC value, equal to 70.99 %. Contrariwise, logistic regression had the lowest overall performance.

Conclusion

ML models, specifically XGBoost, achieved accurate AF prediction in 3,985 individuals utilizing only twelve clinical-routine data.Evaluation results of each used model.ROC curve and AUC value of each model.
Myocardial determinants of Functional limitation in advanced Fabry cardiomyopathy
Authors: Guida G , Attanasio A , Disabato G , Tondi L , Paglione G , Castelvecchio S , Iannotta M , Bandera F , Spagnolo P , Guazzi M , Lombardi M , Camporeale A , Piepoli M F
Published: October 2024

Background

Cardiac involvement in Fabry Disease (FD) manifests as left ventricular hypertrophy (LVH) often complicated by myocardial fibrosis and/or inflammation. Both LVH and advanced tissue alterations can be non-invasively detected and quantified by cardiac magnetic resonance (CMR) with Late Gadolinium Enhancement (LGE). Impairment in functional capacity has been previously reported in FD patients. However, there is limited data regarding the determinants of myocardial alterations in exercise intolerance in FD.

Methods

Among 190 consecutive FD patients referred for CMR, 41 simultaneously performed a cardiopulmonary exercise test (CPET) to evaluate functional capacity. All patients underwent an extensive CMR protocol to provide a detailed evaluation of cardiac morphology and function, including multiparametric tissue characterization. CPET parameters were compared between patients with advanced Fabry cardiomyopathy (Group B), characterized by hypertrophy, inflammation, and fibrosis, and FD patients without irreversible cardiac damage (Group A).

Results

Group B patients were older compared to Group A (57.0 years vs 33.5 years, p<0.001), had a greater LVH (LVMI: 117 g/sqm vs 76.5 g/sqm, p<0.001; LVMWT 17 vs 10 mm, p<0.001). LV ejection fraction was preserved in both groups but Group B patients had a lower peak VO2 value compared to group A (17.8 ml/kg/min vs 21.9 ml/kg/min, p=0.025), a lower (but not significant) percent-predicted peak VO2. A negative linear correlation was identified between the LGE extension (expressed as % of LV mass) and peak VO2 (r=-0.553, p=0.014). This correlation remained consistent even after excluding patients under chronic beta-blocker therapy (r=-0.678, p=0.045). No significant correlation between LV mass and peak VO2 was found.

Conclusions

in patients with FD, the presence of advanced tissue alterations detected by LGE is associated with reduced functional capacity (low peak VO2) despite preserved LV ejection fraction, with a significant negative correlation.
Association of lifes essential 8 and mortality among adults with and without CVD
Authors: Kobo O , Kaur G , Gulati M , Mamas M
Published: October 2024

Background

Differences in the American Heart Association’s Life’s Essential 8 (LE8) score and its association with mortality based on the presence of clinically prevalent cardiovascular disease (CVD) has not been assessed previously.

Methods

Data from the National Health and Nutrition Examination Survey (NHANES) 2009-2018 was utilized to calculate LE8 scores among adult patients, stratified by the presence of existing CVD. Health metrics were further divided into health behaviors and health factors. Scores were also evaluated based on sex, age, race/ethnicity, and socioeconomic status. Cox proportional hazard models were used to evaluate the association between the levels of cardiovascular health (CVH) and risk of all-cause and cardiovascular mortality.

Results

25,359 patients were included in the analysis, of which 10.2% had known CVD. Individuals with known CVD had lower overall CVH (55.9 vs. 65.8, p <0.001), health behaviors (60.6 vs. 67.9, p <0.001), and health factors (51.3 vs. 63.8, p <0.001) scores. The lower CVH scores in those with prior CVD persisted after stratification by sex, age, race/ethnicity, and socioeconomic status. When assessing the association of CVH metrics with mortality, for every 10-point increase in LE8 score, there was a significant reduction (17%-27%) in all-cause and CV mortality in those with and without CVD.

Conclusions

Individuals with known CVD have lower CVH metric scores. Overall, the LE8 score is able to predict future CV outcomes in both individuals with and without CVD and highlights the importance of effective implementation strategies that target health factors and behaviors in primary and secondary prevention populations.
LE8 score in relation to cardiovascular disease and mortality in individuals with diabetes
Authors: Li W , Xing A , Xu W , Guo L , Gao X , Zhou S , Drouin-Chartier J P , Wu S , Chen Z
Published: October 2024

Background

Evidence regarding the potential health effects of Life’s Essential 8 (LE8) score among individuals with type 2 diabetes (T2D) is limited.

Purpose

We aimed to examine the associations of LE8 score with risk of cardiovascular disease (CVD) and mortality, among individuals with T2D.

Methods

We prospectively followed 19,915 Chinese participants with T2D at baseline or diagnosed during follow-up (Kailuan Study: 2006-2020), who were free of CVD at diagnosis of diabetes. Diet, lifestyle, and health conditions were repeatedly assessed every 2 years. The LE8 score (range, 0-100), was calculated based on 8 components: diet quality, physical activity, smoking status, sleep health, BMI, blood lipids, blood glucose, and blood pressure. We used time-varying cox models to model the associations.

Results

During a median follow-up of 11.5 years in participants with T2D, there were 3,295 incident CVD cases and 3,123 deaths. Higher LE8 score was associated with lower risk of CVD incidence and total mortality among participants with diabetes. The multivariate-adjusted hazard ratios and 95%CIs for the highest quintile of LE8 score compared with the lowest quintile were 0.56 (0.53, 0.59) for CVD incidence, 0.57 (0.53, 0.62) for heart disease incidence, 0.53 (0.49, 0.57) for stroke incidence, and 0.73 (0.69, 0.78) for total mortality (all p trend<0.001). Furthermore, compared with participants with stable or decreased LE8 score after diabetes diagnosis, those with increased LE8 score had 17%-42% lower risk of CVD incidence, heart disease incidence, stroke incidence, and total mortality. These associations persisted in subgroup analysis stratified by age, sex, BMI, smoking status, alcohol intake, family history of diabetes and CVD, and follow-up time.

Conclusions

Higher LE8 score was associated with a substantially lower risk of CVD incidence and total mortality among adults with T2D. These findings further support the tremendous benefit of adhering to a high CVH, defined as the LE8 in reducing the subsequent burden of cardiovascular complications and improving overall health in individuals with T2D.Main TableMain Figure
Progress in understanding the genetic underpinning of coronary artery disease: from genotype to phenotype
Authors: Sa D , Mendonca M , Serrao M , Sousa F , Abreu G , Henriques E , Freitas S , Rodrigues M , Borges S , Guerra G , Ornelas I , Drumond A , Sousa A C , Palma Dos Reis R
Published: October 2024

Background

The functional dissection of genetic risk opens the door to strategies for pharmacological manipulation of molecular and cellular processes implicated in human diseases, including coronary artery disease (CAD).

Aim

To assess the relationship between a set of single nucleotide polymorphisms previously associated with CAD and coronary artery calcium (CAC) score in an asymptomatic population from Portugal.

Methods

Prospective study in a cohort of 1,284 subjects aged 59.3±8.9 years, 73.6% males without apparent CAD. The CAC score was performed by cardiac computed tomography and reported as Agatston units according to the Hoff nomogram. Anthropometric, conventional, and biochemical risk factors were evaluated. Thirty-three single nucleotide polymorphisms were genotyped by TaqMan real-time PCR. Bivariate and multivariate logistic regression analysis estimated variables associated with the CAC score.

Results

After bivariate analysis, PHACTR1 rs1332844 C>T, a downstream regulator of the endothelin-1 gene, showed a significant association with CAC score (p=0.015), together with CDKN2B-AS1 variants rs4977574 A>G in the locus 9p21.3 (p=0.002) and rs1333049 G>C (p=0.010). MTHFD1L gene encodes a mitochondrial enzyme responsible for homocysteine remethylating in methionine, and rs6922269 G>A showed protection against artery calcification (p=0.013). After multivariate logistic regression, PHACTR1 rs1332844 (CT+TT) (p=0.009) and CDKN2B-AS1 rs4977574 A>G (GG) (p=0.002) remained in the equation as independently associated with arterial calcification, together with male sex (p=0.039), age (p<0.0001), hypertension (p=0.001), diabetes (p<0.0001), smoking status (p<0.0001) and obesity (p=0.020). MTHFD1L rs6922269 AA also remained as significant protection from arterial calcification (p=0.027).

Conclusion

The present work showed two genetic variants, PHACTR1 and CDKN2B-AS1, linked to arterial wall calcification, herewith clinical and environmental risk factors. MTHFD1L showed protection. Understanding the genetic basis of vessel calcification can enable lifestyle changes or pharmacologic therapy to attenuate risk before the disease becomes clinic. More research in this field is critical to understanding the genetic basis of CAD through an intermediate phenotype, coronary arterial wall calcification.
Is genetic information helpful in predicting recurrent events in young patients after acute coronary syndrome?
Authors: Sousa F , Mendonca M I , Sa D , Abreu G , Henriques E , Freitas S , Rodrigues M , Borges S , Guerra G , Drumond A , Sousa A C , Palma Dos Reis R
Published: October 2024

Coronary Artery Disease (CAD) shares environmental and genetic factors. Young patients with acute coronary syndrome (ACS) carry a poor long-term prognosis. The clinical utility of genetic information in predicting CAD events remains unknown.

Aim

Evaluate the clinical utility of a multiplicative Genetic Risk Score (mGRS) to predict lifelong residual risk in CAD patients below 55 years with few risk factors.

Methods

475 non-diabetic patients with LDL cholesterol levels below 100mg/dL at the first admission who suffered a prior MI at age ≤55 years were followed prospectively for a mean of 5.6±5.3 years. A mGRS was performed with nine variants associated with CAD but not with traditional risk factors (TRF): CDKN2B-AS1 (rs1333049 and rs4977574), TCF21 (rs12190287), PHACTR1 (rs1332844), MIA3 (rs17465637), ADAMTS7 (rs3825807), ZC3HC1 (rs11556924), SMAD3 (rs17228212) and GJA4 (rs618675). The mGRS was subdivided into terciles. Using Cox regression analysis, the predictive and discriminative score ability for events was evaluated. C-statistic discriminated cardiovascular events occurrence. Whether mGRS was included in the TRF model, Net Reclassification Improvement (NRI), or Integrated Discrimination Improvement (IDI) reclassified patients. Kaplan-Meier method estimated survival curves.

Results

There were 153 patients with at least one cardiovascular event. The bivariate analysis showed the strongest correlation with second and third mGRS tercile, multivessel disease, left ventricular dysfunction, and inflammation. Multivariate Cox regression HR adjusted for events was 1.44 (p=0.103) for the intermediate and 2.00 (p=0.001) for the high-risk tercile. The mGRS inclusion improved C-statistic (∆C-index=0.010; p=0.004), NRI (35.4%; p<0.0001) and IDI (2.7%; p=0.0005).

Conclusions

Our 9-SNP mGRS better identified and reclassified younger CAD patients with a high probability of cardiovascular events, improving clinical decision-making and reducing costs for therapeutic strategies.
A systematic review and meta-analysis on the predictive value of the C2HEST score to predict new onset atrial fibrillation in >11 million Western and Asian subjects
Authors: Pastori D , Menichelli D , Li Y G , Brogi T , Pignatelli P , Farcomeni A , Lip G Y H
Published: October 2024

Background

The incidence of new-onset atrial fibrillation (NOAF) is increasing in the last decades. NOAF is associated with worse long-term prognosis. The C2HEST score has been recently proposed to stratify the NOAF risk. The C2HEST score includes coronary artery disease or chronic obstructive pulmonary disease (1 point each), hypertension (1 point), elderly (age ≥ 75 years, 2 points), systolic heart failure (2 points), thyroid disease (1 point). Pooled data on the performance of the C2HEST score are lacking, as well as its performance in different subgroups of patients.

Methods

Systematic review and metanalysis of observational studies reporting data on NOAF according to the C2HEST score. We searched PubMed, Web of Science and Google scholar databases. Metanalysis of the area under the curve (AUC) with 95% confidence interval (95%CI) was performed. We performed a sensitivity analysis on 1) subjects from the general population/primary care and 2) patients with cardiac disease, 3) Asian patients, 4) Western patients. The risk of bias (RoB) analysis was performed with the Cochrane RoBINS tool for observational studies, evaluating the following domains: bias due to confounding, to selection of participants, in classification of interventions, to deviations from intended interventions, due to missing data, in measurement of outcomes and in selection of the reported result.

Results

Strategy search retrieved 360 articles. Of these, 17 studies were included, accounting for 11,067,496 subjects/patients with 307,869 NOAF cases. Mean age ranged from 41.3 to 71.2 years. The pooled analysis gave an AUC of 0.70 (95%CI 0.66-0.74) with high heterogeneity. A subgroup analysis on studies from general population/primary care yielded an AUC of 0.69 (95%CI 0.64-0.75). In the subgroup of patients with cardiovascular disease, the AUC for the C2HEST score was 0.71 (0.69-0.79). The C2HEST score performed similarly in Asian (AUC 0.72, 95%CI 0.68-0.77), and in Western patients (AUC 0.68, 95%CI 0.62-0.75).

We also performed a metanalysis of the Hazar ratios (HR) for different cut-offs of the C2HEST score. A C2HEST score >1 yielded an HR of 3.98 (95%CI 2.40-6.60), a C2HEST score >2 an HR of 5.63 (95%CI 2.78-11.42) and a C2HEST score >3 an HR of 5.02 (95%CI 2.64-9.54).

Conclusion

The C2HEST score shows a good performance in predicting NOAF in primary and secondary prevention studies. Furthermore, its predictive value is similar between Western and Asian subjects, making it widely usable in clinical practice. More data in other high-risk subgroups of patients such as those with stroke and after cardioversion-ablation patients are needed.
The MADIT-ICD benefit risk score for Japanese patients -from Nippon Storm study-
Authors: Kondo Y , Takanashi Y , Nada T , Nitta T , Aizawa T , Ohe T , Kurita T
Published: October 2024

Background

Implantable cardioverter-defibrillators (ICDs) play a crucial role in preventing sudden death due to lethal arrhythmias such as ventricular tachycardia and ventricular fibrillation. However, like any medical intervention, ICD implantation is not without its complications. It is essential to carefully consider the risks and benefits, and appropriately stratify the risk of sudden death in order to make informed decisions. In 2020, the MADIT-ICD benefit risk score was proposed to utilize personalized integrated assessment of the competing risk of lethal arrhythmias vs. non-arrhythmic mortality in implantable cardioverter-defibrillator (ICD) candidates.

Purpose

To evaluate the risk stratification of using the MADIT-ICD benefit risk score in Japanese patients.

Methods

We analyzed the data of 451 patients, enrolled in the Nippon Storm Study, with left ventricular ejection fraction (LVEF) ≤35% who underwent ICD implantation for primary prophylaxis of sudden cardiac death (men, 78%; age, 65±12 years; LVEF, 25±6.4%; cardiac resynchronization therapy, 73%; ischemic cardiomyopathy (ICM), 33%).

Results

A total of 336 patients were enrolled iln this study. The MADIT-ICD benefit risk scores, except systolic blood pressure, was calculated (Figure 1). These patients were classified into 3 groups (Lowest, Intermediate, Highest). There were no significant differences between the three groups in all-cause mortality, cardiovascular death, non-arrhythmic death, and appropriate ICD therapy (Figure 2). The multivariate analysis demonstrated that LVEF ≤25% was significantly associated with all-cause mortality, cardiovascular death, non-arrhythmic death (p=0.0487, 0.0150, 0.0387).

Conclusion

The MADIT-ICD benefit risk score may not be appropriate to risk stratification in Japanese patients using ICD for primary prophylaxis.Figure 1Figure 2