Coronary Heart Disease Research Articles

Independent associations of educational attainment and its joint associations with LE8 score for risk of cardiovascular disease incidence and mortality among Chinese people

Abstract Background/Introduction Educational attainment is a social determinant of health. Quantifying its associations with risk of cardiovascular disease (CVD) incidence and mortality has public health importance. Recently, the American Heart Association introduced the Life’s Essential 8 (LE8) score to evaluate CVD risk. However, it remains unclear how educational attainment and the LE8 score interact in their joint associations with CVD and mortality. Purpose To examine the associations of educational level with the incidence of CVD, including coronary heart disease (CHD) and stroke, and total mortality. Also, we examined the joint associations of educational level and the LE8 score with CVD incidence and total mortality. Methods We prospectively followed 91,744 Chinese adults from the Kailuan Study (2006-2021), who were free of CVD at baseline. Information on educational level, diet, lifestyle, and health conditions was collected every 2 years. LE8 score was calculated based on eight components: diet quality, physical activity, smoking status, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. We used time-dependent Cox models to assess the associations of educational level with the outcomes as well as the joint associations of educational level and LE8 score, with adjustments for demographics, dietary and lifestyle factors, and medical history. Results During a mean follow-up of 13.1 years, there were 12,916 incident CVD cases and 13,090 deaths. Compared with the participants who only received illiteracy or elementary education, those who received high school education and above had a lower risk of CVD incidence (HR = 0.82, 95% CI = 0.76, 0.88), stroke incidence (0.72, (0.66, 0.79)), and total mortality (0.73, (0.68, 0.77)). Educational level was not associated with risk of CHD. Furthermore, significant additive interactions between educational attainment and LE8 score on the risk of CVD and mortality were observed (all p values for additive interactions <0.01). Compared with the participants who only received illiteracy or elementary education and had a low LE8 score, those who only received illiteracy or elementary education but had a high LE8 score still had a 27%-47% lower risk of CVD and total mortality, while those who received high school education and above and had a high LE8 score had a 51%-74% lower risk of CVD and total mortality. Conclusions Higher educational level was associated with a lower risk of CVD and mortality. These inverse associations were most apparent among participants with both a high educational level and a high LE8 score, while the participants with a low educational level but with a high LE8 score still had a significantly lower risk. These findings highlight the importance of improvement in educational attainment in preventing CVD events and deaths, and suggest that CVD events and deaths attributable to lower levels of education may be reduced by improving LE8 score.

Relation of apolipoprotein C3 to risk of major adverse cardiovascular events and death after acute coronary syndrome on a background of optimized statin treatment

Abstract Background Apolipoprotein C3 (ApoC3), a component of triglyceride-rich lipoproteins and some low-density lipoprotein and high-density lipoprotein particles, has been shown to predict incident coronary heart disease (CHD) and major adverse cardiovascular events (MACE). However, it is unknown whether ApoC3 predicts risk in patients with acute coronary syndrome (ACS) receiving contemporary therapies including optimized statin treatment, and if any such association is independent of apolipoprotein B (ApoB) levels. Purpose We assessed the association of ApoC3 with first MACE (CHD death, nonfatal myocardial infarction, fatal or nonfatal ischaemic stroke, or hospitalization for unstable angina) and all-cause death in patients with recent ACS treated with high-intensity or maximum-tolerated statin and blinded PCSK9 inhibitor (alirocumab, ALI) or placebo (PBO). Methods ApoC3 was measured by mass spectrometry at baseline (n=11,956) and after 4 months (M4; n=11,176) of treatment with ALI or PBO in the ODYSSEY OUTCOMES trial (which had 18,924 total participants). In continuous and spline analyses adjusted for treatment group and ApoB, we assessed the association of baseline ApoC3 with risk of MACE and death. In the ALI group we determined association of change in ApoC3 from baseline to M4 with risk of MACE and death after M4 in a model adjusted for baseline ApoC3 and ApoB, and the change in ApoB from baseline to M4. Results Median (Q1, Q3) baseline ApoC3 concentration was in a normal range [85 (65, 113) mg/L]. Continuous ApoC3 was not related to MACE (p=0.50) or death (p=0.51); spline analysis showed a slight curvilinear association of baseline ApoC3 with risk of MACE and death, but no clinically meaningful relationship (Figure). Findings were similar in the PBO group alone, and without adjustment for ApoB (data not shown). At M4, the median (Q1, Q3) change from baseline in ApoC3 was -10 (-27, -5; p<0.0001) mg/L with ALI and 2 (-14, 18; P = NS) mg/L with PBO. Overall, ALI significantly reduced the incidence of MACE (10.1% vs 12.1%; p=0.0006) and death (3.5% vs 4.2%; p=0.045) compared with PBO among those with available baseline ApoC3. However, the change in ApoC3 on treatment with ALI did not predict the risk of MACE or death after M4. Findings were qualitatively similar without adjustment for ApoB or its change. Conclusion In a cohort with recent ACS receiving optimized statin therapy and with median baseline ApoC3 in a normal range, ApoC3 did not provide clinically meaningful prediction of cardiovascular events or death. A modest reduction of ApoC3 by ALI did not associate with subsequent risk of MACE or death. It remains uncertain whether targeted therapies producing larger reductions in ApoC3 from higher baseline levels will affect cardiovascular risk.

Triglyceride-glucose index predicts the prognosis of patients with ischemic cardiomyopathy

Abstract Objective A large number of studies have provided strong statistical evidence that the Triglyceride-glucose (TYG) index is associated with the development and prognosis of cardiovascular disease. However, little is known about the predictive value of TYG index for ischemic cardiomyopathy (ICM). This study aimed to investigate the predictive value of TYG index in patients with ICM. Methods Hospitalized patients ICM in our Hospital from April 2014 to December 2017 were included in this study. Inclusion criteria: previous definite diagnosis of coronary atherosclerotic heart disease (coronary angiography found one or more vessels stenosis > 50%) and echocardiography showed LVEF < 45 percent. In addition, the TYG index was calculated as follows :LN[fasting triglycerides (mg /dl)× fasting blood glucose (mg /dl)x1/2]. The endpoint of the study was MACE events, including all-cause death, myocardial infarction, ischemia-induced revascularization and heart failure (HF) rehospitalization. Results A total of 688 patients were included in this study and followed up for 1 year. In the multivariate Cox proportional hazards model, TYG index (adjusted HR 2.33 [95% CI: 1.30-4.20], P<0.01) were associated with an increased risk of MACE events, and the area under the ROC curve (AUC) was 0.604 (95%CI: 0.528-0.680, p <0.05). A total of 197 ICM patients with previously diagnosed diabetes were screened for analysis. We found that TYG index (adjusted HR 6.63 [95% CI: 2.15-20.47], P<0.01), and the AUC was 0.691 (95%CI: 0.562-0.820, p<0.05). Conclusion TYG index can predict the poor prognosis of ICM patients, and the predictive value of TyG index for ICM patients with diabetes is more significant.

Normal values and reference ranges for quantitative assessment of myocardial first-pass perfusion by spectral computed tomography. From the Cadami-Spectral study

Abstract Background Spectral computed tomography (SCT) can generate iodine concentration maps according to the tissue iodine uptake, serving as a surrogate marker of organ perfusion. Thus, assessment of the iodine distribution maps derived from SCT allows to detect deviations in normal myocardial perfusion. As of present, reference ranges for the iodine concentration in each myocardial segment of the left ventricle (LV) derived from the first-pass perfusion have not been published. Purpose To provide normal values of first pass perfusion in individuals without coronary artery disease (CAD). Additionally, we explored whether these values could vary according to gender, contrast dosing or the cardiac cycle phase assessed. Methods From October 2021 to January 2024, we retrospectively identified patients who underwent a CT Cardiac Angiography (CTCA) and had no evidence of CAD or structural heart disease. Subjects were scanned using a dual-layer SCT, following a standard local protocol which included a weight-based contrast medium dosing of 0.8 mL/Kg. Iodine density maps were reconstructed using the MCA filter at a phase of 78%. An additional sample of 18 subjects who received a dosing of contrast of 1 mL/Kg and 16 cases scanned using a systolic acquisition and reconstructed at phase of 35% were also included. Spectral reconstructions were combined with tissue segmentation to obtain the spatial distribution of iodine along the myocardium. Mean, median and standard deviations values of density of iodine (mg/ml) were quantified for each segment following the AHA-17 segment model. Results Perfusion data from 80 woman (median age: 60 [IQR: 54-65.6] years) and 47 males (median age: 47 [IQR: 43 – 54] years) were analysed. Despite receiving higher dose of contrast (67.9 vs 59.8 mL; p < 0.05), male subjects exhibited lower iodine density values in the myocardium compared to females (median concentration per segment 1.58 vs 2.01 mg/dL, p<0.001; figure 1). Notably, the volume of the LV myocardium was higher in male than in women (143 mL vs 92 mL, p<0.001). These differences could be partially explained in a mixed model considering the ratio contrast dose/myocardium volume (b = 1.500, p < 0.001). Higher contrast dosing (1 mL/Kg vs 0.8 mL/kg) correlated with higher iodine density values in the myocardium (2.03 vs 1.83 mg/dL, respectively; p = 0.023). No differences were noted when comparing reconstructions at systole vs diastole (1.86 vs 1.80 mg/dL, respectively; p = 0.484). Reference range values of each myocardial segment are listed in table 1. Conclusions Significant gender discrepancies are detected in the analysis of first-pass myocardial perfusion. These variations can be partially explained by differences in the LV myocardium volume. Our findings provide applicable reference ranges of the iodine concentration in myocardium at first pass perfusion in controls without coronary or structural heart disease.

Diabetes and the risk of cardiovascular events and all-cause mortality among older adults: an individual participant data analysis of five prospective studies.

Guidelines and studies provide conflicting information on whether type 2 diabetes (T2D) should be considered a coronary heart disease risk (CHD) equivalent in older adults. We synthesized participant-level data on 82,723 individuals aged ≥65 years from five prospective studies in two-stage meta-analyses. We estimated multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of T2D (presence versus absence) on a primary composite outcome defined as cardiovascular events or all-cause mortality. Secondary outcomes were the components of the composite. We evaluated CHD risk equivalence by comparing outcomes between individuals with T2D but no CHD versus CHD but no T2D. The median age of participants was 71 years, 20% had T2D and 17% had CHD at baseline. A total of 29,474 participants (36%) experienced the composite outcome. Baseline T2D was associated with higher risk of cardiovascular events or all-cause mortality versus no T2D (HR 1.44, 95% CI [1.40-1.49]). The association was weaker in individuals aged ≥75 years versus 65-74 years (HR 1.32 [1.19-1.46] vs. 1.56 [1.50-1.62]; p-value for interaction = .032). Compared to individuals with CHD but no T2D, individuals with T2D but no CHD had a similar risk of the composite outcome (HR 0.95 [0.85-1.07]), but a lower risk of cardiovascular events (HR 0.76 [0.59-0.98]). T2D was associated with increased risk of cardiovascular events and all-cause mortality in older adults, but T2D without CHD conferred lower risk of cardiovascular events compared to CHD without T2D. Our results suggest that T2D should not be considered a CHD risk equivalent in older adults.

Time trends in mortality, incidence and case-fatality of acute myocardial infarction in Norway - do we see the end of the coronary heart disease epidemic?

Abstract Background In Norway and most industrialized countries the mortality rates from acute myocardial infarction (AMI) increased after World War II, peaked in the 1960s – 1970s, and have since that time declined (Figure). Recent studies have suggested that the decline may have leveled off, and that the favourable trends do not include younger age groups, possibly due obesity and diabetes. Also, the relative contribution of a reduction in incidence and improved case-fatality rates (CFR) to the AMI mortality trends are not known with certainty. We examined mortality trends of AMI in Norway during 1951 – 2021, and the incidence and CFR of hospitalized and non-hospitalized AMI during 2013-2021. Methods Fatal AMI cases were identified in the National Causes of Death Registry. Norwegian hospitals are required by law to register all patients hospitalized for AMI in the Norwegian AMI Registry. Hospitalized cases not registered in the AMI registry were retrieved from the Norwegian Patient Registry which contains discharge diagnoses for hospitalized patients. The national unique 11-digit identification number allowed linkage of the registries and identification of transfers between hospitals and re-hospitalizations. An AMI (either hospitalization or death) was classified as incident if no hospitalization was found for that individual during the previous 5 years. We calculated age-adjusted rates with the Norwegian population in 2017 as standard. Results Norwegian AMI mortality rates increased from 1951, peaked in the late 1960s, and have since that time declined steadily, although steeper after around 1990 (Figure). Present AMI mortality rates are lower than in the 1950s, and are still declining. Incidence of AMI (hospitalized and non-hospitalized) fell from 391/100 000 in 2013 to 271/100 000 in 2021, corresponding to a mean reduction of 3.6 % per year (p<0.001). Incidence of out-of-hospital fatal AMI fell by 6.5 % per year, incidence of hospitalized ST-segment elevation AMI (STEMI) fell by 2.3 % per year, and incidence of non-ST-segment elevation AMI (NSTEMI) fell by 3.1 % per year (all p<0.001). 30-days CFR of hospitalized and non-hospitalized AMI fell from 21.3 % in 2013 to 17.5 % (3.6 % per year; p<0.001). CFR after NSTEMI fell from 8.2 % in 2013 to 6.4 % in 2021 (4.4 % per year; p<0.001), whereas there was no significant change in CFR after STEMI (13.3 % in 2013 and 12.0 % in 2021). The incidence and CFR trends were similar in men and women aged 20-49, 50-79 and 80+ years. Comments Declining incidence of out-of-hospital fatal AMI and declining incidence of hospitalized STEMI and NSTEMI were major contributors to the declining AMI mortality rates in Norway. Improved case-fatality rates among hospitalized patients have contributed to the declining mortality rates, but there was no improvement in case-fatality in STEMI during 2013-2021.

Predictive value of Type D personality combined with unhealthy cardiovascular behaviors for the long-term adverse cardiovascular events in ACS patients

Abstract Background Acute coronary syndrome (ACS) has become a major public health problem worldwide due to its high morbidity and mortality. In addition to traditional risk factors, psychosocial factors play an important role in the development of ACS.Type D personality, as a combination of social inhibition and negative affect, has been defined as a psychological risk factor for coronary heart disease by the European Society of Cardiology.Meanwhile, ACS patients with Type D personality may have behaviors such as unhealthy dietary behaviors, less regular physical activity, and poorer self-management behaviors. Then, whether the combination of Type D personality and poor cardiovascular health behaviors can increase the risk of poor prognosis in patients with ACS requires further research. Purpose The aim of this study was to investigate the effect of Type D personality combined with poor cardiovascular health behaviors on long-term major adverse cardiovascular events(MACE) in patients with ACS. Methods A total of 18631 patients diagnosed with ACS between January 2017 and July 2023 were included in this study. Type D personality, cardiovascular health behaviors (smoking cessation, physical activity, average sleep duration at night, dietary assessment index, BMI, lipids, blood glucose, blood pressure) were assessed during the admission period, and were divided into poor, general, and ideal cardiovascular health with a cut-off score of 50 and 80.The binary logistic regression analysis was used to assese the effect of Type D personality combined with cardiovascular health score on the occurrence of MACE (stroke, reinfarction, revascularization, all-cause death). Results The median follow-up in this study was 37 months, and we found that a total of 3750 people had MACE during the follow-up period. The logistic regression result showed that compared with Type D personality (-) and cardiovascular health behaviors (poor) group, Type D personality (+) and cardiovascular health behaviors (poor) group (OR=1.451, 95%CI=1.055-1.995,P=0.022), Type D personality (+) and cardiovascular health behaviors (general) group (OR=1.425, 95%CI=1.092-1.858,P=0.009), Type D personality (-) cardiovascular health behavior (poor) group (OR=1.301, 95%CI=1.013-1.670, P=0.039) were independent risk factors for the occurrence of further adverse cardiovascular events. Conclusion Type D personality combined with unhealthy cardiovascular behavior individuals may be at high risk for MACE. Therefore, early assessment of Type D personality and cardiovascular health behaviors are needed, thereby reducing the incidence of MACE in ACS patients.

Routine application of cardiac magnetic resonance imaging in patients with suspected myocarditis from immune checkpoint inhibitor therapy

Abstract Background Cardiovascular adverse events including myocarditis associated with immune checkpoint inhibitor (ICI) therapy remain a challenge in clinical practice. Diagnostic assessment of ICI-related myocarditis (ICI-M) is challenging due to a variable phenotype, confounding effects and limited sensitivity of diagnostic tools. Cardiac magnetic resonance imaging (CMR) is used to diagnose non-ICI myocarditis, but evidence on diagnostic sensitivity is low, particularly in patients with a discrete phenotype. Here, we aim to assess the impact of CMR in patients with suspected ICI-related myocarditis and relate to final diagnosis including endomyocardial biopsy findings. Methods All consecutive patients receiving CMR for suspected ICI-M between September 2019 and January 2024 were included and retrospectively analysed. CMR parameters were correlated with clinical, laboratory and echocardiographic parameters and stratified for presence or absence of myocarditis as per final diagnosis. Results A total of 55 patients who received CMR for suspected ICI-related myocarditis were analysed, including 25 patients with confirmed ICI-M as per final diagnosis and 30 patients with cardiotoxicity other than myocarditis or no cardiotoxicity (ICI-O). The mean age (ICI-M versus ICI-O) was 65.7±13.6 versus (vs.) 67.3±9.9 (p=0.61) years, 32.0% vs. 26.7% (p=0.67) were female, and 40.0% vs. 26.7% (p=0.29) had pre-existing coronary heart disease. Cardiac biomarkers and echocardiographic data did not differ between the groups. In CMR analysis, presence of late gadolinium enhancement (LGE) was associated with ICI-M (56.0% vs. 26.7%, p=0.027). Myocardial oedema was generally rare and not associated with ICI-M. Endomyocardial biopsy (EMB) was used in 6 out of 55 patients (10.9%) with suspected ICI-M. In 4 of these 6 patients (66.7%) EMB confirmed ICI-M diagnosis. Of note, only 2/4 patients with EMB-confirmed myocarditis showed abnormal CMR findings. Conclusion The diagnostic assessment of ICI-M is challenged by low sensitivity of common diagnostic measures, often requiring a multimodal approach. Presence of LGE in CMR was associated with ICI-M, but sensitivity and specificity are low. Our data emphasize the high value of EMB in patients with clinically suspected ICI-M despite inconspicuous CMR. Prospective data to improve diagnostic criteria are needed.

Social differences in subclinical coronary artery atherosclerosis in Sweden

Abstract Most data indicate an inverse relation between socioeconomic status and clinically manifest coronary heart disease that is only partly explained by modifiable cardiovascular risk factors. Few population-based studies have investigated social factors with respect to differences in subclinical coronary atherosclerosis in a healthy population without prior manifest coronary disease. Purpose To examine socioeconomic differences in imaging-detected coronary atherosclerosis, and to which extent potential differences could be explained by modifiable risk factors. Methods The Swedish CArdioPulmonary bioImage Study (SCAPIS) randomly invited individuals aged 50 to 64 years from the general population. Out of 30,154 participants, we defined a population of healthy participants without prior myocardial infarction or coronary procedures, with technically satisfactory results from coronary computed tomography angiography (CCTA) and coronary artery calcification scoring (CACs). CCTA outcomes were recorded as 1. any coronary atherosclerosis, 2. coronary stenosis ≥50%, 3. segment involvement score (SIS) ≥4, and 4. coronary artery calcium score (CACs) ≥100. Results Among 24,616 participants (49.2% women, mean age 57.4 (SD 4.2) years), those with ≤9 compared to ≥12 years of education were heavier, with mean (SD) BMI 28.0 (4.5) compared to 26.1 (4.0) kg/m2, with more hypertension (23.3% vs 15.0%), and diabetes (9.6% vs 4.6%), and with more active smokers (17.4% vs 3.8%). The prevalence of plaque/significant stenosis is shown in the Figure. Findings with respect to low vs high education and odds ratios (ORs) adjusted for age and sex were: 48.8% vs 35.3% for any coronary atherosclerosis, OR 1.31; 95%CI 1.19-14.4; 6.8% vs 4.4% for coronary stenosis ≥50%, OR 1.21; 95%CI 0.99-1.47; 15.7% vs 9.8% for SIS≥4, OR 1.21; 95% CI 0.99-1.47; and 10.1% vs 7.1% for CACS≥100, 1.29; 95%CI 1.12-1.48 (Table). However, after adjustment for coronary risk factors no significant associations with subclinical coronary atherosclerosis persisted. Conclusions After adjustment for conventional modifiable risk factors there was no convincing evidence of any independent association between low education and subclinical coronary atherosclerosis. Further studies are needed to explore which other mechanisms could potentially explain an independent link between low socioeconomic status and clinically manifest coronary heart disease.Figure

Long-term exposure to PM2.5 and mortality among Japanese community-dwelling adults

Abstract Background Long-term exposure to PM2.5 (particulate matter with a diameter of 2.5 μm or smaller) is a risk factor for mortality and cardiovascular disease including stroke. However, there was limited evidence for the association between PM2.5 exposure and stroke in Asia where the major cardiovascular disease is stroke. Additionally, the causal association between PM2.5 and respiratory disease is still unresolved. The aim of this study was to investigate the association between long-term exposure to PM2.5 and all-cause, cardiovascular, and respiratory disease mortality in a Japanese community-based prospective cohort. Methods This study included 46,974 participants (19,707 men; 27,267 women) from the second cohort of the Ibaraki Prefectural Health Study. The participants were followed up from baseline survey (in 2009) to 31 December 2019. We confirmed underlying causes by death certificates. Using the PM2.5 concentrations estimated by the inverse distance weighting methods based on ambient air monitoring data, administrative area level concentrations were assigned to each participant. The hazard ratios (HRs) and 95% confidence intervals (CIs) of mortality using a Cox proportional hazard model were presented. Results We identified 2,789 all-cause deaths during the 470,178 person-years of follow-up. PM2.5 exposure had no significant association with all-cause and cause-specific mortality. The multivariable-adjusted HRs per 1 μg/m3 increase in the PM2.5 concentration were 0.94 (95% CI = 0.80-1.12) for coronary heart disease, 0.92 (95% CI = 0.81-1.04) for stroke and 1.09 (95% CI = 0.97-1.23) for non-malignant respiratory disease. Conclusions We observed little evidence of increased risk of all-cause and cause-specific mortality by long-term exposure to PM2.5 whose concentrations ranged from 8.3 to 13.1 μg/m3. A somewhat increased trend for non-malignant respiratory disease mortality may not be negligible. Key messages • We found little evidence of increased risk of all-cause and cause-specific mortality by long-term exposure to PM2.5. • Somewhat increased tendency for non-malignant respiratory disease mortality associated with PM2.5 exposure was observed.

Plasma levels of human growth differentiation factor 15 (GDF-15) and their effect of alirocumab on major adverse cardiovascular events and all-cause death after acute coronary syndrome

Abstract Background Human growth differentiation factor 15 (GDF-15) is a stress response cytokine of the transforming growth factor-β superfamily with roles in health and disease, cell survival and inflammation, and whose elevated plasma levels impair muscle metabolism and cause cachexia. GDF-15 also may play multiple roles in the pathophysiology of cardiovascular disease. Methods The ODYSSEY OUTCOMES trial compared the PCSK9 inhibitor alirocumab to placebo added to high-intensity or maximum-tolerated statin in patients post-acute coronary syndrome (ACS). We assessed in >11,000 patients for whom biobank samples were available, the relation between GDF-15 levels (Roche Diagnostics) at baseline and at 4 months with risk of major adverse cardiovascular events (MACE; primary endpoint, comprising coronary heart disease death, non-fatal myocardial infarction, fatal/non-fatal ischaemic stroke, unstable angina requiring hospitalization) and all-cause death, with adjustment for age and sex. Results Median GDF-15 (quartile [Q]1, Q3) at baseline was 1022 (755, 1465) pg/mL and was reduced by a placebo-adjusted median of 22 pg/mL with alirocumab (p=0.0009) at month 4. This lowering of GDF-15 by alirocumab may represent the first such report via pharmacotherapy. In the placebo group, baseline GDF-15 was significantly associated with risks of MACE (Figure Panel A) and death (Panel B). Relative risk reduction with alirocumab did not vary according to baseline GDF-15 levels for MACE (Panel C) and death (Panel D). Four-year MACE absolute risk reduction [ARR (95% CI)] with alirocumab at Q1 and Q3 of baseline GDF-15 was 2.0% (0.1%, 3.9%) and 2.6% (0.2%, 5.0%), respectively. Reduction of GDF-15 with alirocumab at month 4 was not associated with subsequent MACE (p=0.46) but was associated with death (p=0.0009), with greater reductions translating to lower risk. Conclusion In patients with recent ACS, GDF-15 is a strong predictor of both MACE and death. Reduction of GDF-15 with alirocumab at month 4 was not associated with subsequent MACE but was associated with death (p=0.0009), with greater ARR reductions translating to lower risk. Figure. Splines for baseline GDF-15 vs risk of MACE (Panel A; spline p<0.0001) or all-cause death (Panel B; spline p<00001) through 4 years in the placebo group; treatment hazard ratio for MACE (Panel C; spline p=0.52) and all-cause death (Panel D; spline p=0.78). All splines reflect adjustment for age and sexFigure

NICE guidance in the rapid access chest pain clinic: does it work?

Abstract Background Rapid Access Chest Pain Clinics (RACPC) were developed following the publication of the National Service Framework for Coronary Heart Disease in 2000(1). The National Institute for Health and Care Excellence (NICE) produces guidelines for the management of patients with recent onset chest pain of suspected cardiac origin(2). In 2016 the guidance was updated and recommended the use of CT coronary angiography (CTCA) as the initial investigation for patients with chest pain which was typical or atypical of angina. Adherence to the guideline may be dependent upon factors such as local availability of CT scanners and clinician preference. The RACPC in this tertiary centre is nurse-run with no medical involvement. There is good engagement with the CT department and in July 2017 the NICE guidance was adopted in the clinic. Purpose To evaluate the use of CTCA as the first line investigation for patients with typical or atypical chest pain. Methods Data from all patients reviewed in the clinic between 01/07/2017 and 31/12/2023 were prospectively collected, entered into a database, and then retrospectively analysed. The data were organised into 3 groups: patients with typical chest pain; atypical pain and those with non-cardiac sounding chest pain. The number of patients in each group who underwent a CTCA, and the outcome of the scan were evaluated. The CT scans were categorised as showing significant coronary artery disease (CAD), non-obstructive CAD, no CAD, or as inconclusive. The outcome of patients who had a positive CTCA was also recorded. Results 2986 patients were reviewed in the RACPC in the above period. 14.2% of patients presented with typical pain, 47.4% with atypical pain, and 30.6% had non-cardiac pain. The remaining patients presented with other symptoms such as breathlessness. CTCA was used as the first investigation in the majority of patients with typical or atypical pain, unless alternative investigations or management were deemed to be more clinically appropriate. In 59.5% of typical and 78.5% of atypical presentations, the CT scan showed no CAD, or non-significant CAD. There was a low incidence of positive scans in both groups, however patients with typical pain were more likely to have significant CAD (Table). All patients who had a CTCA indicating significant CAD, were referred for invasive angiography. 88.0% of typical presentations, and 64.0% of those with atypical pain, underwent revascularisation. No patient who underwent invasive angiography was found to have normal coronary arteries. Conclusion Atypical pain is the most frequent presentation in the RACPC, however the majority of these patients, and most of those with typical pain, do not have significant CAD. Careful assessment and the use of CTCA as the initial investigation, enable the identification of those patients who need invasive angiography. This is a cost-effective strategy which also reduces risk and radiation exposure for patients.

Heart failure and advanced chronic kidney disease: differences in characteristics, treatment and outcomes in patients with glomerular filtration rate greater or less than 30 ml/minute/m2

Abstract Introduction Heart failure (HF) is a serious health problem and continues to have a high mortality and incidence of decompensation, despite advances in its management. Chronic kidney disease (CKD) is very prevalent in patients with HF, hinders their treatment and worsens their prognosis, especially when it is advanced CKD (glomerular filtration rate-GFR <30 ml(min/m2). It is important to know the differential characteristics of these patients to improve their management. Purpose To analyze in a contemporary registry of HF patients followed in specialized HF units in Spain the differences in clinical characteristics and treatment between patients with HF and advanced CKD. Methods We analyzed data from the registry of the SEC-Excelente-IC quality accreditation program of the Spanish Society of Cardiology, with 1716 patients with HF included between 2019 and 2021 by 45 specialized HF units accredited by the SEC. Patients were included consecutively in two 1-month cutoffs (March and October) in that period. The clinical and demographic characteristics and comorbidities of the patients were compared according to GFR < or > 30ml/min/m2. Results Of the 1,716 patients, 11.1% had a GFR<30 and 88.9% >30 mL/min/m2. Figure 1 shows the main clinical characteristics and comorbidities of the 2 groups. Median LVEF was similar in both groups: 42 (30-58) vs 38% (29-54). The group with advanced CKD was older (77±9.6 vs 70.5±12.6 years; p<0.001), had greater HF severity (more admissions for HF in the last year, worse NYHA functional class and longer evolution time), and a higher prevalence of coronary heart disease, hypertension, diabetes mellitus, cognitive impairment, anemia, iron deficiency and hyponatremia. There were no differences in sex, BMI, serum potassium or other comorbidities (Figure 1). Figure 2 shows the treatment received in each group. Patients with GFR <30 received in a significantly lower proportion all drugs for HF (p<0.001), except diuretics and potassium binders (ACEI/ARA, sacubitril-valsartan, MRA, beta-blockers, digoxin and SLGT2 inhibitors), and less cardiac rehabilitation (5.2 vs 10.4%; p=0.029). Incidence of one-year mortality was significantly higher in patients with GFR<30 ml/min/m2 (37.2 vs 14.4 per 100 persons-year, p<0.001), as were HF hospitalizations (61.3 vs 33.0; p<0.001) and HF decompensations without hospitalization (24.1 vs 11; p<0.001). Conclusions In our contemporary cohort of real-life HF patients, the prevalence of advanced CKD was 11.1%. These patients had a higher severity of HF, despite which, the utilization of HF drugs, including SGLT2 inhibitors was much lower than in those with GFR >30 ml/min/m2. One-year mortality, HF hospitalization and HF decompensations were almost 3-times higher. This treatment trend needs to be modified to improve the prognosis of these patients.

Unraveling the paradox: the impact of one or more traditional risk factors on short-term mortality following acute coronary syndromes.

Abstract Background It has been recently suggested that individuals without exposure to any standardized modifiable risk factors may have an increased risk of all-cause mortality from acute coronary syndromes (ACS) compared with their counterparts with one or more risk factors, including diabetes. Purpose To estimate the individual contribution of the four traditional risk factors to the risk of adverse outcomes from first ACS. Methods We analyzed data from 70,953 Caucasian patients presenting with first ACS, but without prior coronary heart disease in the International Survey of Acute Coronary Syndromes (ISACS) Archives registry network from October 2005 to January 2021. The primary outcome was all-cause mortality within 30 days after hospital admission. We calculated sex-specific risk ratios (RRs) stratifying traditional risk factors, current smoking, diabetes, hypercholesterolemia and hypertension into mutually exclusive categories using a balancing strategy by inverse probability weighting. Results Compared with patients presenting without risk factors, those with diabetes had significantly higher 30-day mortality in both women (RR, 1.29; 95% CI, 1.06-1.57) and men (RR, 1.40; 95% CI, 1.16-1.69). By contrast, patients who were current smokers or presented with a history of hypercholesterolemia or hypertension had significantly lower 30-day mortality than patients with no risk factors with RRs ranging from 0.53; 95% CI 0.42–0.67 in women who were smokers to 0.46; 95% CI 0.37–0.59 in men with hypercholesterolemia. The impact of diabetes on mortality was obscured in patients who concomitantly presented with diabetes and one more traditional risk factor. The RRs in combination with current smoking were 1.39; 95% CI 0.92 -2.09 in women and 0.89; 95% CI 0.68 -1.17 in men; with hypercholesterolemia: 0.91; 95% CI 0.66 -1.25 in women and 0.75; 95% CI 0.53–1.06 in men; with hypertension: 1.14; 95% CI 0.99–1.32 in women and 1.12; 95% CI 0.96–1.31 in men. Conclusions Diabetes confers a significant independent excess mortality risk at 30 days following ACS. Dilution bias in this setting refers to the weakening of the observed effect of diabetes because of the inclusion of "one more" risk factor with lower risk profile. Potential misinterpretation of the relationship between diabetes and death from ACS may negatively affect healthcare organization

Real-world evidence for patient phenotypes in heart failure with preserved ejection fraction

Abstract Background Heart failure (HF) with preserved ejection fraction (HFpEF) presents a high mortality risk due to its heterogeneous and multifactorial nature, coupled with limited treatment options. The incompletely understood pathophysiology is influenced by various comorbidities, resulting in different clinical phenotypes. Identifying these could be crucial for tailored HFpEF treatments. While previous studies focused on small, well-characterized patient populations, electronic health records (EHRs) offer the potential to unveil HFpEF phenotypes in larger real-world patient groups. Purpose We aimed to establish a sizable, unselected HFpEF patient population using real-world data. Employing cluster analysis, we intended to uncover distinct groups with varied disease aetiology and medical needs based on comorbidity profiles and prognoses. Methods From EHRs of n = 1,610,101 HF patients, we identified an HFpEF cohort of n = 32,009 patients, by applying thresholds for the LVEF and data availability, and by excluding confounding conditions. Clustering by the relative frequency of common comorbidities aimed to reveal patient populations with unique prognoses, comorbidity profiles, and clinical and demographic characteristics. Results Six clusters of different sizes, comorbidity prevalence, clinical presentation, and all-cause mortality were identified. About 50% of patients (n = 15,445) were predominantly hypertensive, with varying extents of coronary heart disease and diabetes mellitus (DM), and a 5-year mortality of about 30%. Around 22% (n = 7,089) exhibited a cardiometabolic comorbidity profile, with an increased prevalence of obesity and sleep apnea, but also DM and hypertension, and a 5-year mortality of 22.5%. Over 15% of patients (n = 5,298) had a 5-year mortality rate of 45.0%, marked by highest rates of anaemia and chronic kidney disease (CKD) but also DM, elevated N-terminal prohormone of brain natriuretic peptide levels, and a reduced estimated glomerular filtration rate. Conclusion Despite the favourable prognosis, a significant proportion of patients represent a cardiometabolic HFpEF phenotype with notable unmet medical needs regarding cohort size and multimorbidity. Patients simultaneously suffering from CKD, anaemia, and the highest mortality rates may represent a previously underrecognized phenotype. Our study demonstrates that distinct medical needs can be identified in a large, unselected real-world HFpEF cohort. In contrast to clinical trials, this approach enabled access to a broader patient population, revealing novel phenotypes to be targeted by precision medicine in the future.

Chronic kidney disease in patients with heart failure in German primary care practices: the InspeCKD study

Abstract Background Chronic kidney disease (CKD) is, alongside type 2 diabetes mellitus, the most common comorbidity in patients with heart failure (HF), with a prevalence of 40-50%. HF patients should therefore be screened, monitored, and treated according to international Kidney Disease Improving Global Outcomes (KDIGO) conclusions for early identification and intervention of CKD, with annual determination of eGFR to monitor kidney function and annual urine albumin-to-creatinine ratio (UACR) testing as appropriate. Early diagnosis is important as therapeutic options can be offered to slow the progression of CKD and reduce the risk of cardiovascular complications and mortality. Purpose Currently, there are only limited data available regarding screening, diagnosis and treatment of CKD for HF patients in German primary care physician (PCP) practices. Therefore, this analysis of the InspeCKD study was designed to examine the frequency of use of CKD-specific laboratory diagnostics in HF patients in routine PCP care. Methods In the current data analysis, fully anonymized patient data from German PCP practices were evaluated. In accordance with the screening recommendation of the KDIGO guideline, adult patients with diabetes, hypertension and/or cardiovascular disease, including HF, with at least one year of observation period were included in the analysis. Results The overall patient cohort comprised 448.837 patients from 1.244 German PCP practices. Of the 7.9% HF patients, 6.1% participated in a disease management program (DMP) for coronary heart disease. The average age of HF patients was 74 years. The prevalence of diagnosed CKD in HF patients during the observational period (mean: 1.7 years) was 26.8%. Within the subgroup of patients with HF, serum creatinine to estimate GFR was measured at least once in 48.5% of patients. Urine dipstick testing for albuminuria was performed in 7.4% of patients and UACR was measured at least once in 0.3% of patients. In patients with at least one documented measurement, eGFR and UACR were checked 2.2 and 0.9 times, respectively, per patient and year. Of the HF patients with laboratory-confirmed CKD according to KDIGO criteria, 81.8% were not diagnosed with CKD. Conclusion The analysis shows that, given the high prevalence of CKD in HF patients and the current KDIGO recommendations for early identification and intervention of CKD, a substantial proportion of HF patients in German PCP practices did not receive adequate laboratory diagnostics for early diagnosis of CKD. In addition, the majority of patients with laboratory-confirmed CKD were not diagnosed. Early detection of CKD and the use of evidence-based therapeutic options can significantly reduce the risk of CKD progression. In conclusion, there is an urgent need to raise awareness among PCPs about secondary and tertiary prevention of CKD in patients with HF and to include coordinated CKD screening recommendations in HF guidelines.

Metabolomic profiling of the entire UK Biobank enables interpretation of familial hypercholesterolemia mutations and prediction of severe cardiovascular outcomes

Abstract Background Familial hypercholesterolemia (FH) is an inherited disorder resulting in high levels of LDL-C from birth. Premeature coronary heart disease occurs in half of affected men by age 50 years(1). While many genetic variants that cause FH are well understood, there are also many variants in FH genes that are of uncertain clinical significance. Furthermore, the variability in residual cardiovascular risk of FH carriers after statin treatment is not fully understood. We here investigate whether metabolomic and genomic data from the 500,000 person UK Biobank cohort can aid in interpretation of candidate pathogenic variants for FH, and characterise future risk of severe cardiac events in the carriers of such variants. Methods We have quantified 249 metabolomic parameters in 490,830 blood samples from UK Biobank cohort. Among 186,483 participants with exome sequence data we identified 896 who carried known pathogenic FH variants and 405 who carried variants of unknown significance in an established FH gene. We fitted a logistic predictive model to identify pathogenic mutations using LDL levels, statin use and 17 principal components of the metabolomic parameters. We further tested whether metabolomic and genomic scores for predicting future risk of myocardial infarction (MI), that were trained in the general population (i.e. individuals without FH), could predict risk in FH carriers. Results A model including all metabolites had a higher accuracy at identifying known pathogenic FH variants (36/56 at FDR < 0.05), compared to LDL and statin use alone (30/56). Our model also identified 8 FH variants marked as uncertain significance in ClinVar with significant (FDR < 0.05) evidence of predicted pathogenicity. We found that our metabolomic risk score predicted 10-year risk of MI among FH carriers (HR=1.96 per SD, p = 0.0011). This was indeed stronger than the effect in the general population (HR = 1.64 per SD, p = 2.5e-168). A combined metabolomic and polygenic risk score had an even larger effect at predicting MI in FH carriers (HR = 3.06 per SD, p = 2.0e-6), and this score was significantly better at predicting MI in FH carriers than in non-carriers (HR = 3.06 vs 1.88 per SD, interaction p = 0.042). Conclusion Familial hypercholesterolemia is an important source of risk for early cardiovascular disease. Population-scale metabolomics can help distinguish pathogenic from benign variants that have not yet been characterised. Metabolomic and genomic scores can also identify individuals at most elevated risk, and provide even more information to FH individuals than in the general population.

The Relationship of Duffy Gene Polymorphism with High-Sensitivity C-Reactive Protein, Mortality, and Cardiovascular Outcomes in Black Individuals

Background: Black adults have higher incidence of all-cause mortality and worse cardiovascular disease (CVD) outcomes when compared to other U.S. populations. The Duffy chemokine receptor is not expressed on erythrocytes in a large majority of Black adults, but the clinical implications of this are unclear. Methods: Here, we investigated the relationship of Duffy receptor status, high-sensitivity C-reactive protein (hs-CRP), and mortality and incident CVD events (coronary heart disease, stroke, and heart failure) in self-identified Black members of three contemporary, longitudinal cohort studies (the Women’s Health Initiative, Jackson Heart Study, and Multi-Ethnic Study of Atherosclerosis). Data on 14,358 Black participants (9023 Duffy-null and 5335 Duffy-receptor-positive, as defined using single-nucleotide polymorphism (SNP) rs2814778) were included in this analysis. Results: Duffy null was strongly associated with higher hs-CRP (meta-analysis p = 2.62 × 10−9), but the association was largely attenuated, though still marginally significant (p = 0.005), after conditioning on known CRP locus alleles in linkage disequilibrium with the Duffy gene. In our discovery cohorts, Duffy-null status appeared to be associated with a higher risk of all-cause mortality and incident stroke, though these associations were attenuated and non-significant following adjustment for traditional risk factors including hs-CRP. Moreover, the association of Duffy-null status with mortality could not be replicated in an independent sample of Black adults from the UK Biobank. Conclusions: These findings suggest that the higher levels of hs-CRP found in Duffy-null individuals may be in part independent of CRP alleles known to influence circulating levels of hs-CRP. During the follow-up of this community-based sample of Black participants, Duffy-null status was not associated with mortality or incident CVD events independently of traditional risk factors including hs-CRP.

Analysis of risk factors for the development of major adverse cardiovascular and cerebrovascular events in patients after aortic valve replacement with myocardial revascularization

Background. Acquired aortic valve disease and coronary heart disease often occur together, and almost two thirds of patients with aortic valve stenosis have severe coronary heart disease. Given the presence of both pathologies, this cohort of patients requires an individual diagnostic and therapeutic approach. The aim of the study was to analyze risk factors for the development of major adverse cardiovascular and cerebrovascular events (MACCE) in patients after aortic valve replacement with myocardial revascularization. Materials and methods. For this study, a selection of disease histories of adult patients (over 18 years old) who underwent surgical aortic valve replacement (SAVR) together with myocardial revascularization at the State Institution “Heart Institute of the Ministry of Health of Ukraine” from 2018 to 2022 was carried out. Results. We selected 130 case histories of patients who underwent SAVR together with myocardial revascularization: the first group (n = 51) — a combination of SAVR and percutaneous coronary interventions; the second group (n = 79) — a combination of SAVR and coronary artery bypass grafting. The analysis of intraoperative data showed that the duration of cardiopulmonary bypass and aortic cross-clamping in patients of the first group was significantly lower, by 1.5 times (p = 0.0001) and 1.4 times (p = 0.0001), compared to the second group. There was no significant difference between the study groups regarding the frequency of MACCE (p = 0.589). Reliable risk factors for the development of MAССE in the early postoperative period were the evaluation of the operative risk according to the EuroSCORE II scale (odds ratio (OR) 2.13, confidence interval (CI) 1.54–4.48, p = 0.012), the history of myocardial infarction (OR 1.43, CI 1.13–2.45, p = 0.002) and right coronary artery damage (OR 1.79, CI 1.44–3.78, p = 0.021). Conclusions. Patients who underwent percutaneous coronary interventions before SAVR were characterized by a shorter duration of cardiopulmonary bypass and aortic cross-clamping, however, no significant difference in major early postoperative complications was observed between the study groups. In particular, there were no significant differences regarding the frequency of MACCE in the early postoperative period.

Cardio-metabolic disorders in a patient with non-alcoholic fatty liver disease and normal body weight

The relationship between the formation of non-alcoholic fatty liver disease (NAFLD) in obese individuals has been proven, which increases the patient’s cardio-metabolic risk. A number of studies have demonstrated that patients with normal body weight (NBW) have comparable risks of developing cardiovascular disease and progression to NAFLD compared to obese patients. Purpose of the study: To assess the incidence of cardio-metabolic disorders in patients with NAFLD and NBW. Materials and methods: 225 patients of both sexes (18–65 years old) with confirmed NAFLD were included. Patients were divided into 3 groups according to body mass index (BMI) values. Results: In patients of group 1, an increased risk of developing coronary heart disease (CHD), arterial hypertension (AH), type 2 diabetes mellitus and progression of liver fibrosis was revealed with an increase in the level of the triglyceride index. Conclusions: The study demonstrated the need for early identification of NAFLD in NBW individuals and assessment of existing cardiometabolic risk factors.