Occurrence Of Myocardial Infarction Research Articles

Abstract 4135025: Inflammation-related 5-hydroxymethylation signatures as markers for clinical presentations of coronary artery disease

Background: Coronary angiography, an invasive method, remains the gold standard technique for coronary artery disease (CAD) diagnosis in clinical practice. However, due to its invasive nature, it cannot be used for mass population screening. There is an urgent need in the clinical to identify new liquid biopsy molecular markers for screening patients with CAD. Methods: We utilized 5hmC-Seal to generate genome-wide 5hmC profiles in plasma cell-free DNA (cfDNA) from 724 CAD patients. To investigate the correlation between 5hmC modifications and CAD, we separated patients into training and validation cohorts and developed a 5hmC-based logistic regression model from the training cohort to predict CAD patients in the validation cohort. Furthermore, we incorporated an external cohort comprising 167 samples to validate the reliability of our model. Results: We found that the differentially hydroxymethylated genes (DhMGs) in people with the normal coronary artery (NCA), nonfatal stable CAD (sCAD), non-ST-elevation myocardial infarction (NSTEMI), as well as ST-elevation myocardial infarction (STEMI) enriched in neutrophil-mediated inflammatory response pathways, and inflammation-related DhMGs can reflect the progression of atherosclerotic plaque. Furthermore, we used machine learning algorithms to develop a predictive model for predicting the occurrence of myocardial infarction (MI) based on 19 inflammatory markers, and the predictive model could effectively predict MI (NSTEMI and STEMI) (AUC = 0.913). Simultaneously, our model has demonstrated strong performance in external validation. Conclusions: We have identified a novel biomarker, the inflammation-associated 5hmC markers, which can reflect the clinical manifestations of CAD and can effectively predict the occurrence of MI.

Abstract 4138333: Childhood Oral Health Associates with the Incidence of Ischemic Heart Disease, Myocardial Infarction and Ischemic Stroke in Adulthood

Introduction: Cardiovascular disease remains a considerable source of years of life lost. Thus, identification of possible risk factors and prevention strategies continues to be important. In adults, oral diseases are associated with the risk of cardiovascular disease, including ischemic heart disease (IHD), myocardial infarction (MI) and ischemic stroke (IS). Few studies have examined the effect of oral health in childhood on the risk of cardiovascular disease in adulthood, thus overlooking a potentially important avenue of early detection of high-risk individuals. Hypothesis: We hypothesize that poor childhood oral health is associated with IHD, MI, and IS in adulthood. Methods: Using nationwide Danish registry data from the National Child Odontology Register, National Patient Register, and the Central Person Register we followed individuals born between 1963 and 1972. Follow-up started in 1995 or by age 30 (whichever occurred last), and ended in 2018, where study participants were aged 46 to 56. Using Cox-proportional hazards modelling we examined the association of childhood oral health, defined as the highest registered level of dental caries and gingivitis for any one individual, with the occurrence of IHD, MI, and IS in adulthood. The highest achieved level of education between ages 25 and 30 was used as Cox-strata. Results: The study consisted of n = 569.057 individuals, 51.2% male, 48.8% female. The incidence of IHD was 26% (1.17; 1.86) higher in females with high levels of caries in childhood compared to those with low-level caries, 19% (1.08; 1.40) higher in males. Severe caries in childhood was associated with a 58% (1.19; 2.09) higher incidence of MI in females, 19% (1.01;1.42) higher in males, and a 45% (1.19; 1.78) higher incidence of IS, 52% (1.27; 1.81) in males. Females had a 52% (1.19; 1.94) higher incidence of MI, and males a 32% (1.15; 1.52) higher incidence of IS, if they had high levels of gingivitis as children (table 1). Conclusion: Poor oral health in childhood is associated with an increased incidence of IHD, MI, and IS, pointing to a potential new avenue for early identification of and prevention amongst high-risk individuals.

Amelioration of Systemic Amyloidosis by Blocking IL-17A and Not by IL-17F, and Arteriosclerosis by Blocking Both IL-17A and IL-17F in an Inflammatory Skin Mouse Model.

There are comorbidities and complications in atopic dermatitis and psoriasis that often occur after the appearance of skin inflammation. Statistically, data show that patients with psoriasis and atopic dermatitis have a shorter life expectancy than patients without psoriatic dermatitis, due to the occurrence of arteriosclerosis, myocardial infarction, and cerebral infarction. Many types of skin inflammation are treated with various antibody preparations, and marked improvement in patients' quality of life can be achieved. The next theme is to understand the pathogenesis of arteriosclerosis, myocardial infarction, stroke, and other complications associated with dermatitis and to find treatments and drugs to reduce their occurrence. The skin, a crucial immune organ, generates large amounts of inflammatory cytokines in response to various stimuli, leading to systemic inflammation and potential damage to internal organs. The link between inflammatory skin conditions like psoriasis and atopic dermatitis with serious health complications such as vascular disorders and systemic amyloidosis has been increasingly recognized. In psoriasis, biological treatments targeting Interleukin (IL)-17A, a key cytokine, have shown promise in reducing cardiovascular risks. Recent developments include treatments that target both IL-17A and IL-17F in the psoriasis field, though each cytokine's impact on internal organ damage is still under debate. Among visceral complications secondary to dermatitis, systemic amyloidosis and atherosclerosis have been reported to be controlled by suppressing IL-17 in the early stages of dermatitis. Still, it remains unclear whether suppressing IL-17 prevents organ damage in the late stages of persistent severe dermatitis. A study using a long-lasting dermatitis mouse model that overexpressed human caspase-1 in keratinocytes (Kcasp1Tg) investigated the effects of deleting IL-17A and IL-17F on visceral complications. Cross-mating Kcasp1Tg with IL-17A-, IL-17F-, and IL-17AF-deficient mice assessed the skin and visceral organs histologically, and RT-PCR analysis of aortic sclerosis markers was performed. Despite less improvement in dermatitis, deletion of IL-17A in Kcasp1Tg mice showed promising results in reducing multiple organ amyloidosis. On the other hand, the effect was observed in both IL-17A and IL-17F deleted mice for aortic sclerosis. The inhibition of IL-17A and IL-17F was suggested to reduce the risk of developing comorbidities in internal organs. IL-17A and IL-17F were found to act similarly or produce very different results, depending on the organ.

Overview of the risk of myocardial infarction in patients with aortic stenosis: insights from the VALVENOR Registry

Abstract Background Close interaction between aortic stenosis (AS) and coronary artery disease (CAD) has been suggested. However, the risk of myocardial infarction (MI) in patients with AS is poorly described outside the context of aortic valve replacement. Objectives To assess the incidence, correlates and impact on outcomes of MI occurrence in patients with different degrees of AS severity. Methods Between 2016 and 2017, the multicenter prospective VALVENOR registry enrolled 2,830 outpatients with native valvular AS (peak aortic jet velocity (Vmax) ≥ 2.5m/s). AS was defined as mild (Vmax 2.5-2.9), moderate (Vmax 3-3.9) or severe (Vmax ≥4). MI was defined using the 4th universal definition (type 2 MI were not considered). Results The mean age was 76.0 years, 54% of the patients were men and 18.3% had experienced prior coronary event (PCE). Altogether, one third (n=820 [30.3%]) of the patients had diabetes. At 5 years, the cumulative incidence of MI (death as competing event) was only 2.5% (n=72, 1/3 of ST-elevation MI). Sixty MI (83.3%) were categorized as type 1 MI while 12 were peri-procedural MI (surgical aortic valve replacement, n=5; transcatheter aortic valve replacement, n=2; coronary artery bypass surgery, n=1; percutaneous coronary intervention, n=3; coronary angiography, n=1). PCE and angina symptoms were associated with an increased risk, whereas female gender with a decreased risk. By contrast, AS severity was not associated with the risk of MI. Five-year cumulative incidence of MI was 6.5% [95% CI, 4.5 - 8.9] in patients with PCE vs. 1.7% [95% CI, 1.2 - 2.3] in patients with no PCE (P<0.001), 8.3% [95% CI, 4.1 - 14.4] in patients with angina vs. 2.3% [95% CI, 1.8 - 2.9] in patients without angina (P<0.001), and 3.2% [95% CI, 2.4 - 4.2] in men vs. 1.8% [95% CI, 1.1 - 2.6] in women (P=0.014). Subsequent mortality was high and at 52.8% during follow-up (median 648 days after MI occurrence). When analyzed as a time-dependent variable, incident MI was a powerful predictor of mortality (HR=2.00, P<0.001 after adjustment). Conclusions In patients with AS, the risk of MI is relatively low especially in patients without PCE and without angina. No association between the risk of MI and AS severity was observed. Although rare, incident MI is strongly associated with subsequent mortality.

The effect of 2 years COVID-19 pandemic on myocardial infarction and stroke admissions: nationwide registry study, sex differences and mortality

Abstract Background Throughout the COVID-19 pandemic many countries reported a decline in myocardial infarction (MI) and stroke admissions. Factors leading to the decline remain uncertain. Purpose In this nationwide study spanning the first two years of the COVID-19 pandemic we evaluated the changes in MI and stroke admissions as the effect of pandemic intensity and nationwide lockdown. We also investigated sex and age differences. We benefited from the fact that the Czech Republic had both, the lowest and one of the highest COVID-19 incidence. Methods We compared the first (March 1, 2020, to February 28, 2021) and the second (March 1, 2021, to February 28, 2022) pandemic years overall and during the COVID-19 waves with the preceding year (March 1, 2019, to February 28, 2020). The occurrence of MI and stroke, patient characteristics, and mortality data were obtained from two nationwide registers covering every hospitalization and every death in the Czech Republic. Results During the first and second pandemic year as compared to the preceding year there were 13,856 and 14,123 vs 15,499 MI admissions, representing a -10,6% (p<0.001) and -8,9% (p<0.001) decline; and 23,194 and 23,231 vs 25,046 stroke admissions, representing a -7.4% (p<0.001) and -7.2% (p<0.001) decline respectively. The significant decline appeared in both MI and stroke in all COVID-19 waves (spring 2020, spring 2021, autumn 2020/winter 2021, -autumn 2021/winter 2022). The greatest MI hospitalization decline (-16%) occurred during the first strict national lock down, during the first COVID-19 wave (spring 2020), the pandemic wave with the lowest COVID-19 incidence. Both, MI and stroke admissions reversed to pre-pandemic numbers during the summer (2020, 2021) when most lockdown restrictions were lifted. The decline in MI was greater in women than in men during both the first (-11.8%, -10%; p<0.001) and second (-10.8%, -7.9%; p<0.001) pandemic years, also for stroke in women greater than in men during the first (-9%, -5.9%; p<0.001) and second (-9.7%, -4.8%; p<0.001) pandemic years. The 30-day all-cause mortality in patients with MI was higher during the first (10.6%; p<0.001) but not the second (9.6%; p=0.34) pandemic year as compared to the preceding year (9.3%), whereas the 30-day mortality in patients with stroke remained unchanged. Conclusions There was a decline in both MI and stroke admissions during the first two years of the pandemic, but such decline was not related to COVID-19 incidence. The greatest reduction in both, MI and stroke admissions, appeared during the first lockdown in the first COVID-19 wave (spring 2020), the period of the lowest COVID-19 incidence. Moreover, the decline in MI and stroke admissions was greater in women. This highlights potential sex differences in health effect. Health authorities should be aware of these findings, in order to adapt their message and restriction measures in case of future major epidemics.Myocardial infarction casesStroke cases

Pharmacologic treatment of hypertension guided by non-invasive haemodynamics in primary care improves blood pressure control

Abstract Background Current guidelines on hypertension (HTN) provide blood pressure (BP) targets and therapeutic algorithms but ignore the potential to treat individual patients according to their haemodynamic profile. We have shown that use of non-invasive haemodynamic information obtained by impedance cardiography (ICG) can improve BP control in the primary care setting. Purpose To investigate whether improved rates of BP control by matching patients’ non-invasive haemodynamics to specific pharmacologic treatments and increasing patient engagement translates into improved clinical outcome measures. Methods Electronic medical records (EMR) were obtained for 14,698 patients from two US primary care groups between 2014 and 2023. ICG was done when BP exceeded 140/90 mmHg. Haemodynamic measurements included mean arterial pressure (MAP), cardiac index (CI), cardiac power index (CPI), total peripheral resistance index (TPRI), stroke index (SI) and heart rate (HR) (Figure 1). Haemodynamic ICG profiles were classified as: Vasoconstriction, Hyperdynamic, or Mixed pattern. Printed clinical decision support (CDS) tools and later an EMR integrated CDS application were used to communicate recommendations to physicians. Printed reports were shared with patients to increase their engagement. Pharmacological therapy was tailored based on haemodynamic information. Rates of successful BP treatment and the occurrence of myocardial infarction (MI) or stroke were tracked through the EMR. Results Of 14,698 patients, 50% were women, 17% were Black and 17% were aged 18-49 years, 45% aged 50-69 years, and 38% age ≥ 70 years. A total of 21,246 ICGs were performed classifying patients as Vasoconstriction 47%, Hyperdynamic with high heart rate (HR) or high stroke index (SI) 24%, and Mixed Haemodynamic (combination of Vasoconstriction and Hyperdynamic) 29% (Figure 1). Demographic features were not strongly associated with haemodynamic classification. Within 2-3 years of inclusion, >85% of patient achieved BP control (<140/90 mmHg), which was sustained during follow-up. Over a median (IQR) follow-up of 8 (2016-2023) years, there were 14 (5) MI and 34 (16) strokes. These event rates appear to be lower than those reported in other large cohorts of patients with HTN. Conclusions Treating patients with HTN according to their individual haemodynamic profile is associated with high rates of BP control. Further analysis will determine whether the rates of MI, stroke and death are lower than expected based on the patients baseline risk profile.Haemodynamic Status (ICG Test Results)

The prevalence, patients characteristics and risk factors of hyper-Lp(a)-emia in the Polish population. The first results from the PMMHRI-Lp(a) Registry

Abstract Background Based on the recent data and existing guidelines Lp(a) is recognized, independent CVD risk factor. However, the knowledge on the prevalence of elevated Lp(a) levels, patients characteristics as well as non-genetic risk factors is scarce from some world regions including from Poland, the largest CEE country. Purpose We aim to present the first results from the Lp(a) registry established in the 2nd largest hospital in Poland - Polish Mother’s Memorial Hospital Research Institute (PMMHRI). Methods The PMMHRI-Lp(a)-Registry was established in 2022. The indications for Lp(a) measurement in the registry are based on the 2021 Polish Lipid Guidelines and new Polish recommendations on the management with elevated Lp(a) (2024). The PMMHRI-Lp(a)-Registry is a part of the being founded Lp(a) National Registry of the Polish Lipid Association. Results Based on the data from 302 consecutive patients (mean age 52.18 years; women 53%) the mean Lp(a) level was 30.3±39.4 mg/dl; it was numerically higher in woman (32.8 mg/dl), but there were no significant sex differences (men: 27.5 mg/dl; p=0.245). There were also no significant differences between those with and without CAD, stroke, HF, cancer, diabetes, kidney disease, and thyroid disease. The significant Lp(a) level difference was observed in those with diagnosed dyslipidemia in comparison to those without (31.9±40.6 vs 17.7±25.8 mg/dl, p=0.044) and in those with the history of myocardial infarction (MI) vs those without (50.1±50.3 vs 28.1±37.5 mg/dl, p=0.004). However, when we divided those with MI on premature vs no premature, no significant difference in Lp(a) level was observed (41,6±41.9 vs 57.6±56.7 mg/dl, p=0.39). Lipid lowering therapy did not significantly affect Lp(a) level, with only significant differences in those treated with ezetimibe (as a part of the combination therapy; 39.5±47.6 vs 27.5±36.3 mg/dl, p=0.027). For selected patients (n=31; 10.3%) with two Lp(a) measurements (mean time distance: 7±5 months) we did not observe any significant visit-to-visit variability (mean difference: 0.81 mg/dl; z=0.256, p=0.262) (Fig. 1). We did not also observe any percentage differences in variables (besides MI history, p=0.017) for different Lp(a) risk groups: 0-30, >30-50, >50-180 and >180 mg/dl. While dividing the population on those with Lp(a) ≤30 mg/dl vs >30 mg/dl, the only differences were seen for dyslipidemia diagnosis (p=0.044) and MI occurrence (6.98 vs 17.24%; p=0.007). Similar pattern was observed while dividing the whole population on those with Lp(a) ≤50 vs >50 mg/dl (Fig. 2). Conclusions These results strongly emphasize that Lp(a) should be measured commonly, as its high level is highly prevalent in patients at the risk both in primary and secondary prevention, what require risk re-stratification and treatment optimization. This is especially important in the regions that characterize of baseline high CVD risk, what refers to most of the CEE countries, including Poland.

Effects of short-term exposures to lower air temperature and cold spells on myocardial infarction hospital admissions: a nationwide study in Sweden

Abstract Background Exposures to lower air temperature and cold spells have been associated with an increased risk of various diseases. However, the short-term effect of lower air temperature and cold spells on myocardial infarction (MI) remains incompletely understood. Purpose We aimed to evaluate the short-term effects of lower air temperature and cold spells on MI hospital admissions within the nationwide SWEDEHEART registry. Methods This population-based nationwide study included 120,380 MI cases admitted to hospitals in Sweden during the cold season (October to March) from 2005 to 2019. Daily mean air temperature was estimated at 1 km2 spatial resolution across Sweden using a three-stage machine learning approach and percentiles of daily temperatures experienced by individuals in the same municipality were employed as individual exposure indicators to account for potential geographic adaptation. Cold spells were defined as periods of at least two consecutive days with a daily mean temperature below the 10th percentile of the temperature distribution for each municipality. A time-stratified case-crossover design incorporating a conditional logistic regression model with distributed lag non-linear model using lag 0-1 and lag 2-6 days was employed to evaluate the short-term effects of lower air temperature and cold spells on total MI, non-ST-segment elevation MI (NSTEMI) and ST-segment elevation MI (STEMI). Results We found significant increases in risk for total MI, NSTEMI, and STEMI in association with a decrease of one percentile in temperature at a lag of 2-6 days, indicated by ORs (95% CI) of 1.099 (1.057-1.142), 1.110 (1.06-1.164), and 1.076 (1.004-1.153), respectively. Additionally, we found that cold spells were significantly associated with increased risks for total MI, NSTEMI, and STEMI at a lag of 2-6 days, with ORs (95% CI) of 1.077 (1.037-1.12), 1.069 (1.02-1.119), and 1.095 (1.023-1.172), respectively. Moreover, independent effects of lower air temperature and cold spells on MI occurrence were found after adjusting for each other. Conversely, we observed that lower air temperature and cold spells were associated with decreased risks for MI at a lag of 0-1 days. Conclusions This nationwide case-crossover study demonstrated a novel biphasic pattern in MI risk following exposure to lower air temperatures and cold spells, characterized by an initial transient reduction in risk at lags 0-1 day, followed by a significant increase in risk at lags 2-6 days. As climate change continues to induce complex shifts in regional weather patterns, enhancing protections to reduce future cold-related cardiac hospitalizations is crucial.

Association of contemporary hormonal contraception and the risk of arterial thrombosis

Abstract Background While contemporary hormonal contraception is effective in preventing unwanted pregnancies, its potential link to an increased risk of stroke and myocardial infarction raises safety concerns. Purpose This study aimed to investigate the association between the use of contemporary hormonal contraception and the occurrence of ischemic stroke and myocardial infarction. Methods A nationwide prospective cohort study was conducted, comprising of all Danish women aged 15-49 years without a history of arterial and venous thrombosis, thrombophilia, and cancer from 1996 to 2021. Data on hormonal contraception use, stroke and myocardial infarction diagnoses, and potential confounders were collected from nationwide registers. A Poisson regression analysis was performed adjusting for age, education level, calendar year, hypertension, statin use, diabetes, and atrial fibrillation. Results The study followed 2,205,794 women over 23,700,659 person-years. Weighted median age was 33 (interquartile range (IQR): 24-41) for non-users and 25 (20-34) for users. A total of 5,346 ischemic strokes (22.6 per 100,000 person-years) and 2,351 myocardial infarctions (9.9 per 100,000 person-years) occurred during the study period. When compared to no use, oral contraceptives containing ethinyl estradiol at a dose of 30 to 40 μg was associated with the following adjusted incidence rate ratios (and 95% confidence intervals) for ischemic stroke and myocardial infarction, according to progestin type: levonorgestrel, 1.9 (1.7 to 2.2) and 2.0 (1.7 to 2.4); norgestimate, 1.9 (1.5 to 2.3) and 1.9 (1.4 to 2.6); desogestrel, 2.4 (2.0 to 2.9) and 2.2 (1.6 to 3.0); gestodene, 1.9 (1.7 to 2.2) and 1.9 (1.5 to 2.2); drospirenone, 2.0 (1.6 to 2.5) and 1.8 (1.1 to 2.8); cyproterone acetate, 1.7 (1.2 to 2.3) and 2.1 (1.3 to 3.4), respectively. At a dose of 20 μg of ethinyl estradiol, the incidence rate ratios for ischemic stroke and myocardial infarction varied based on the type of progestin as follows: desogestrel, 1.9 (1.6 to 2.2) and 1.4 (1.0 to 1.9); gestodene, 1.7 (1.4 to 2.0) and 1.7 (1.2 to 2.4); drospirenone, 1.4 (0.7 to 2.6) and 1.1 (0.3 to 4.4); For transdermal patch, the incidence rate ratio was 3.4 (1.4 to 8.2) and 0.0 (0.0 to 0.0); for vaginal ring, 2.2 (1.4 to 3.3) and 3.2 (1.7 to 6.3); for intrauterine device, 1.1 (0.9 to 1.2) and 1.1 (0.9 to 1.3); for implant, 2.0 (1.2 to 3.5) and 1.3 (0.4 to 3.9); for injection, 1.9 (0.9 to 3.8) and 0.6 (0.1 to 4.0). Conclusion Use of contemporary hormonal contraception appeared to be associated with ischemic stroke and myocardial infarction when compared to non-users. The incidence rate ratios varied across type of hormonal contraception, estrogen dose, progestin type and route of administration. The findings underscore the importance of informed decision-making when considering contraceptive options, with implications for public health and individual health choices.FlowchartAdjusted incidence rate ratios

Predictors of adverse cardiac events in a large cohort of patients with antiphospholipid syndrome

Abstract Background Non-valvular cardiac disease in antiphospholipid syndrome (APS) has been modestly evaluated. Aim We wanted to assess the prevalence and evolution of major adverse cardiovascular events(MACE) in a cohort of APS patients. Material and Methods From a large cohort of 181 APS patients included in a study from 2011-2012.year data for the occurrence of MACE in 10 years of follow-up were evaluated in 82 patients (86.6% females, 62.2% with primary (PAPS), and 37.8% patients with APS associated with systemic lupus erythematosus (SLE) (sAPS)). At the inclusion in all patients, a transthoracic echocardiography study for the assessment of dimensions and functionality of the left and right heart along with valvular functions and morphology. Standard atherosclerotic risk factors prevalence was analyzed. Antiphospholipid antibodies(aPL) analysis included the detection of aCL (IgG/IgM), ß2GPI (IgG/IgM), and LA, and all patients were treated according to the valid guidelines by the rheumatologist. Data regarding the occurrence of new myocardial infarction (MI), cerebrovascular events (CVI), arterial and/or venous thrombosis, heart failure (HF), and cardiovascular death (considered as MACE) have been collected 10 years after inclusion. Results The prevalence of standard atherosclerotic risk factors was less than 40% in both study groups. Left ventricle ejection fraction(LVEF) was over 45% in more than 90% of patients in both groups (p=0.246) with valvular dysfunction present in 49% of PAPS and 58.1% of sAPS patients (p=0.426). 9.8% PAPS and 12.9% sAPS had coronary artery disease(CAD) (p=0.724) and HF was present in 7.8% PAPS and 3.2% sAPS (p=0.645). MACE occurred in 17.6% of PAPS and 22.6% of sAPS (p=0.585). The new MI occurred in 9.8% of PAPS and 9.7% of sAPS (p=1.000), CVI in 5.9% of PAPS and 3.2% of sAPS (p=1.000), HF in 5.9% of PAPS and 3.2% of sAPS (p=1.000) and cardiovascular death in 9.8% of PAPS and 12.9% of sAPS (p=0.724). New thrombotic events (arterial and/or venous) occurred in 15.7% of PAPS and 17.2% of sAPS (p=1.000). During the follow-up period, 66.7% of PAPS and 55.2% of SAPS (p=0.313) were treated with aspirin, 25.5% of PAPS and 25.0% of sAPS with warfarin, and chloroquine was administered in 46.8% of PAPS and 53.6% of sAPS (p=0.571). Age (p=0.008), gender (p=0.034), thrombotic APS (p=0.033), hypertension (p=0.003), diabetes mellitus (p=0.043), and cardiovascular manifestations present at the time of APS diagnosis (p=0.035), namely CAD (p=0.001) and HF (p=0.005) were significantly associated with 10y MACE. aPL type and category were not associated with 10y MACE. In a multivariate logistic model, age. hypertension, and HF were independent predictors for 10y MACE. Conclusions APS patients develop new cardiovascular events despite optimal medical therapy. Cardiovascular evaluation at the time of diagnosis and proper cardiologist follow-up with the rigorous treatment of standard atherosclerotic risk factors is of utmost importance.

Negative long-term prognostic value of stress echocardiography in patients with incomplete revascularization after successful primary PCI

Abstract Background The role of stress echocardiography (SECHO) in a risk stratification of patients with incomplete revascularization after primary percutaneous coronary intervention (pPCI) has not been extensively documented. The Aim The aim of our study was to assess the negative long-term prognostic value of SECHO after successful pPCI and incomplete revascularization of non-culprit lesions. Methods Our study consisted of 194 patients (mean age 59±10years, male 136; 70.1%) successfully treated with pPCI, who performed SECHO according to Bruce protocol in order to assess residual ischemia in coronary artery with non-culprit lesion other than treated vessel. Lesion severity of non-culprit coronary arteries was assessed by quantitative coronary angiography. Duke treadmill score, functional capacity (Metabolic Equivalents - METs), achieved target heart rate (THR), chronotropic incompetence, heart rate recovery (HRR), wall motion score index (WMSI) and ejection fraction were calculated in all patients. Slow HRR was defined as ≤18 beats/min. Median follow up of the patients was 96 ± 32.5 months for the occurrence of all-cause mortality and non-fatal myocardial infarction (MI). Results Out of 194 patients, 38 (19.6%) had positive SECHO test, and 7 patients (3.6%) were lost to follow up so they were excluded from further analysis. During the follow-up period 29 out of 149 patients (18.8%) had an adverse event (20 deaths and 9 non-fatal MI). Negative predictive value of SECHO test was 81.2%. Median time from MI to SECHO test was 8 months. Using the Cox regression analysis, univariate predictors of adverse events were slow HRR (HR 3.750 [95% CI 1.620-8.679], p=0.002), Duke score (HR 0.866 [95% CI 0.755-0.994], p=0.040) and chronotropic incompetence (HR 0.310 [95% CI 0.107-0.895], p=0.030). In the multivariate analysis only the slow HRR remained an independent predictor of adverse events (HR 3.329 [95% CI 1.417-7.825], p=0.006). Using the Kaplan-Meier survival curve we see that the patients with slow HRR had much shorter event-free time (slow HRR 117.2 ± 13.4 months vs normal HRR test 139.4 ± 4.2 months, Log Rank 4.988, p=0.026). (Figure 1.) Conclusion SECHO test has excellent negative long-term prognostic value in patients with incomplete revascularization of non-culprit lesions after successful pPCI while patients with slow HRR have more pronounced risk for the occurrence of adverse events.Figure 1.Kaplan-Meier survival curve

Application of anticoagulants in the perioperative period of pci for patients with a history of atrial fibrillation and NSTEMI: a real-world, large multicenter retrospective clinical study

Abstract Backgrounds The optimal management for patients with atrial fibrillation (AF) and concomitant coronary artery disease (CAD) remains unclear, particularly regarding anticoagulants use and ischemia-bleeding balance risks. This study aims to investigate the impact of perioperative anticoagulant use on patients with AF and acute non-ST-segment elevation myocardial infarction (NSTEMI). Methods Data for this study were obtained from a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals from 2010 to 2023. A total of 150,530 patients were enrolled, including 74,373 NSTEMI patients. Patients were divided into anticoagulants and non-anticoagulants groups. A total of 1,358 patients were included in the non-anticoagulant group, and 3,541 patients were included in the anticoagulant group. Patients in each group were one-to-one matched based on propensity scores using the nearest available pair matching (PSM) method with a caliper width equal to 0.01. The primary endpoints were major adverse cardiovascular and cerebrovascular adverse events (MACCE), including cardiovascular death, recurrent myocardial infarction, and stroke. Secondary endpoints included cardiovascular death, recurrent myocardial infarction, BARC type 3 bleeding, and cerebral hemorrhage. Follow-up time points were set at 1 month,3 months, and 6 months. Multivariate Cox regression models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results After PSM matching, each group consisted of 809 patients. The anticoagulant group had a higher proportion of males, a higher prevalence of patients with a history of Percutaneous Coronary Intervention, and hyperlipidemia, while proportions of patients with Killips classification of III/IV and history of chronic kidney disease were lower. Anticoagulant use during the perioperative period significantly reduced the occurrence of MACCE at the primary endpoint at 1 month (aHR 0.57; P < 0.001), 3 months (aHR 0.57; P = 0.023), and 6 months (aHR 0.57; P < 0.001). At the secondary endpoint, anticoagulants use was associated with a lower incidence of cardiogenic death at 1 month,3 months, and 6 months (aHR 0.55; P <0.001), (aHR 0.55; P <0.001), (aHR 0.56; P <0.001), lower risk of myocardial infarction recurrence at 3 months and 6 months (aHR 0.47; P = 0.02), (aHR 0.44; P <0.001), without increasing the risk of bleeding events, including BARC type 3 bleeding and cerebral hemorrhage. Conclusion Perioperative anticoagulant use during PCI can reduce the occurrence of cardiac death, myocardial infarction, and stroke recurrence within 6 months post-surgery without increasing bleeding events in AF and NSTEMI patients. Therefore, for patients with AF, it is recommended to consider combining anticoagulant therapy with dual antiplatelet therapy during the perioperative period, if no contraindications.

Uric acid is associated with increased risk of myocardial infarction: results from NHANES 2009-2018 and bidirectional two-sample Mendelian randomization analysis.

Although a growing number of studies have shown that elevated uric acid (UA) levels are associated with multiple cardiovascular risk factors and progression of coronary artery disease, the causal relationship between UA and the occurrence of myocardial infarction (MI) remains uncertain. The aim of this study was to investigate the relationship between UA and the risk of MI. We screened 23,080 patients in the National Health and Nutrition Examination Survey (NHANES) database for 2009-2018 and explored the association between UA and MI risk using multivariate logistic regression model. In addition, a two-way two-sample Mendelian randomization (TSMR) analysis was performed to examine the causal relationship of UA on MI, and inverse variance-weighted (IVW) results were used as the primary outcome in this study. Sensitivity analysis and horizontal multiple validity test were also performed to verify the reliability of the results. After multivariable adjustment, individuals with the severe elevation of UA levels have a significantly increased risk of MI (OR=2.843, 95%CI: 1.296-6.237, P=0.010). In TSMR analysis, the IVW method demonstrated a significant association between UA and increased risk of MI (OR=1.333, 95%CI: 1.079-1.647, P=0.008). Results from the MR-Egger intercept test, Cochran's Q test, and MR-PRESSO test all suggest the reliability of the IVW analysis. Reverse TSMR analysis did not indicate a causal relationship between genetic susceptibility to MI and UA levels (IVW: OR=1.001, 95%CI: 0.989-1.012, P=0.922). Based on cross-sectional study and Mendelian randomization analysis, it has been demonstrated that UA is an independent risk factor for MI. Elevated levels of UA increase the risk of MI, particularly in cases of severe elevation.

Comparative Analysis of First-Line Antihypertensive Treatment Classes

BackgroundThe best first-line monotherapy for hypertension remains uncertain, as current guidelines suggest that thiazides, angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and calcium channel blockers (CCB) are appropriate in the absence of specific comorbidities. We aimed to compare the outcomes of first-line antihypertensive classes in a real-life setting with a long follow-up period. MethodsThis nationwide retrospective new-user cohort study included patients insured by the largest health maintenance organization in Israel. We included patients with a new diagnosis of hypertension between 2008 and 2021 who initiated treatment with a single first-line drug for hypertension. Outcomes were assessed with and without propensity score matching for confounding factors. The primary composite outcome was the first occurrence of myocardial infarction (MI), acute coronary syndrome (ACS), stroke, or heart failure (HF). ResultsA total of 97,639 patients initiated antihypertensive treatment with a single drug as first-line therapy. The most commonly prescribed class was ACEi/ARB (66,717, 68.3%), followed by CCBs (15,922, 16.3%), beta-blockers (BBs, 12,869, 13.2%), and thiazides (2,131, 2.2%). For the primary outcome, the hazard ratios (HRs) for BBs, CCBs, and ACEi/ARBs were 1.44 (95% CI 1.25 - 1.66), 1.10 (95% CI 0.96 - 1.27), and 1.13 (95% CI 0.99 - 1.29), respectively, when compared to thiazides. ConclusionWhen initiating pharmacotherapy for hypertension with a single drug, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers were associated with similar risk of MI, ACS, stroke, or HF when compared to thiazides, while beta-blockers were associated with increased risk.

Great debate: pre-diabetes is not an evidence-based treatment target for cardiovascular risk reduction.

With the increasing burden of diabetes as a cause of macro- and microvascular disease linked to the epidemics of obesity, attention is being paid to dysglycaemic states that predict and precede the development of type 2 diabetes. Such conditions, termed pre-diabetes, are characterized by fasting plasma glucose, or plasma glucose levels on an oral glucose tolerance test, or values of glycated haemoglobin intermediate between 'normal' values and those characterizing diabetes. These last are by definition associated, in epidemiological terms, with a higher incidence of microvascular disease-mostly retinopathy. Pre-diabetes overlaps with the components of the 'metabolic syndrome'-among which are excess visceral adiposity; hypertension; hypertriglyceridaemia; high levels of small, dense low-density lipoproteins; and metabolic-associated fatty liver disease. There is little doubt that pre-diabetes has important prognostic implications, especially for the occurrence of myocardial infarction, ischaemic stroke, and peripheral arterial disease. It is disputed, however, whether pre-diabetes is itself an actionable disease entity, in addition to the risk factors characterizing it. Because of this uncertainty, the latest European Society of Cardiology guidelines chose not to include pre-diabetes as a treatment target for atherosclerotic cardiovascular disease, at variance from the three previous editions of such guidelines. This is spurring a debate, the Pro and Contra arguments featured in the present debate article.

A combined analysis of bulk RNA-seq and scRNA-seq was performed to investigate the molecular mechanisms associated with the occurrence of myocardial infarction

BackgroundMyocardial infarction (MI) induces complex transcriptional changes across diverse cardiac cell types. Single-cell RNA sequencing (scRNA-seq) provides an unparalleled ability to discern cellular diversity during infarction, yet the veracity of these discoveries necessitates confirmation. This investigation sought to elucidate MI mechanisms by integrating scRNA-seq and bulk RNA-seq data.MethodsPublicly available scRNA-seq (GSE136088) and bulk RNA-seq (GSE153485) data from mice MI models were analyzed. Cell types were annotated, and differential expression analysis conducted. Bulk RNA-seq underwent quality control, principal component analysis, and differential expression analysis.ResultsIn scRNA-seq data, the comparison between MI and sham groups unveiled a reduction in endothelial cell populations, but macrophages and monocytes increased. Within fibroblast subgroups, three distinct categories were discerned, with two exhibiting upregulation in MI. Notably, endothelial cells exhibited an elevated expression of genes associated with apoptosis and ferroptosis. In bulk RNA-seq analysis, distinct patterns emerged when comparing MI and sham groups. Specifically, six genes linked to endothelial ferroptosis exhibited heightened expression in MI group, thereby corroborating the scRNA-seq findings. Moreover, the examination of isolated cardiac macrophages from mice MI model revealed increased expression of Spp1, Col1a2, Col3a1, Ctsd, and Lgals3 compared to sham group, thus substantiating the dysregulation of macrophage apoptosis-related proteins following MI.ConclusionMI altered the transcriptomic landscapes of cardiac cells with increased expression of apoptotic genes. Moreover, the upregulation of macrophage apoptosis marker was confirmed within MI models. The presence of endothelial cell depletion and ferroptosis in MI has been demonstrated.

Exposure to Air Pollutants and Myocardial Infarction Incidence: A UK Biobank Study Exploring Gene-Environment Interaction.

Unraveling gene-environment interaction can provide a novel insight into early disease prevention. Nevertheless, current understanding of the interplay between genetic predisposition and air pollution in relation to myocardial infarction (MI) risk remains limited. Furthermore, the potential long-term influence of air pollutants on MI incidence risk warrants more conclusive evidence in a community population. We investigated interactions between genetic predisposition and exposure to air pollutants on MI incidence. This study incorporated a sample of 456,354 UK Biobank participants and annual mean air pollution (, , , and ) from the UK Department for Environment, Food and Rural Affairs (2006-2021). The Cox proportional hazards model was employed to explore MI incidence after chronic air pollutants exposure. By quantifying genetic risk through the calculation of polygenic risk score (PRS), this study further examined the interactions between genetic risk and exposure to air pollutants in the development of MI on both additive and multiplicative scales. Among 456,354 participants, 9,114 incident MI events were observed during a median follow-up of 12.08 y. Chronic exposure to air pollutants was linked with an increased risk of MI occurrence. Specifically, the hazard ratios (per interquartile range) were 1.12 (95% CI: 1.10, 1.13) for , 1.20 (95% CI: 1.19, 1.22) for , 1.13 (95% CI: 1.12, 1.15) for , and 1.12 (95% CI: 1.11, 1.13) for . In terms of the joint effects, participants with high PRS and high level of air pollution exposure exhibited the greatest risk of MI among all study participants ( to 324%). Remarkably, both multiplicative and additive interactions were detected in the ambient air pollutants exposure and genetic risk on the incidence of MI. There were interactions between exposure to ambient air pollutants and genetic susceptibility on the risk of MI onset. Moreover, the joint effects of these two exposures were greater than the effect of each factor alone. https://doi.org/10.1289/EHP14291.

Prevalence and clinical outcomes of acute myocardial infarction in patients presenting with major trauma

BackgroundThe occurrence and sequelae of acute myocardial infarction (AMI) in major trauma patients is underexplored across both trauma and cardiology specialties. Coronary reperfusion greatly reduces the risk of significant morbidity and mortality in AMI. However, in patients presenting with significant injuries, concurrent AMI presents a competing management priority given the increase in risk of bleeding with standard anticoagulation and antiplatelet therapy, which may be contraindicated. This study aimed to evaluate the epidemiology and clinical outcomes associated with AMI in a contemporary major trauma cohort. MethodsThis study used data from the Victorian State Trauma Registry (VSTR). All adult patients with major trauma from 1 January 2013 to 31 December 2022 were included. Patients that died prior to hospital arrival were excluded. AMI was identified by ICD-10-AM diagnosis codes recorded against the first hospital admission. Clinical outcomes included in-hospital mortality, length of stay, and discharge destination. Results28,928 patients were identified over the 10-year study period. AMI occurred in 401 patients (1.4 %). AMI patients were older, had more comorbidities and were more frequently on anticoagulation or antiplatelet therapy. Low impact fall was the most common trauma mechanism in AMI patients. Patients with AMI experienced longer hospital stays (12 [7–20] versus 7 [4–12] days, p < 0.001) and higher rates of in-hospital mortality (adjusted RR 1.45, 95 % CI 1.25–1.65). ConclusionAMI in the setting of major trauma occurs in an older, more comorbid, and vulnerable group of patients. AMI is associated with an increased risk of in-hospital mortality and prolonged hospital stay in the setting of major trauma, underscoring the importance of identifying and treating major trauma associated AMI in a timely and effective manner.

A cross-sectional study of the association between blood cadmium and mortality among adults with myocardial infarction.

Cadmium (Cd) plays a key role in the occurrence of myocardial infarction (MI). We aimed to explore the association between blood Cd levels and all-cause mortality of MI on the basis of the National Health and Nutrition Examination Survey databases. This study included 800 adults with MI to obtain blood Cd concentrations and their follow-up information. The association between Cd concentrations and mortality was analyzed using Cox regression, restricted cubic spline (RCS) models, mediation analysis, receiver operating characteristic curve, and Kaplan-Meier curves. All the patients were divided into 4 groups according to the quartiles of blood Cd levels (Q1, Q2, Q3, and Q4). Cox regression analysis with adjustment for covariates indicated that Cd was the promoting factor of mortality, and patients with higher Cd had a higher death risk. The RCS model indicated an "inverted checkmark" shaped correlation between Cd levels and mortality, and a turning point of 1.06 μg/L was found. A significant positive correlation was observed on the left of the turning point. Grouped patients by turning point into 2 groups, Kaplan-Meier analysis showed that the low-concentration group had a lower death risk than the high-concentration group. Subgroup analysis revealed that the prognostic effect of Cd was more pronounced in patients with former smoking history, and receiver operating characteristic curve showed that blood Cd had a better-predicting function in patients with MI. Blood Cd levels were significantly related to all-cause mortality in patients with MI, especially in patients with Cd < 1.06 μg/L.

Tailoring Risk Prediction Models to Local Populations.

Risk estimation is an integral part of cardiovascular care. Local recalibration of guideline-recommended models could address the limitations of existing tools. To provide a machine learning (ML) approach to augment the performance of the American Heart Association's Predicting Risk of Cardiovascular Disease Events (AHA-PREVENT) equations when applied to a local population while preserving clinical interpretability. This cohort study used a New England-based electronic health record cohort of patients without prior atherosclerotic cardiovascular disease (ASCVD) who had the data necessary to calculate the AHA-PREVENT 10-year risk of developing ASCVD in the event period (2007-2016). Patients with prior ASCVD events, death prior to 2007, or age 79 years or older in 2007 were subsequently excluded. The final study population of 95 326 patients was split into 3 nonoverlapping subsets for training, testing, and validation. The AHA-PREVENT model was adapted to this local population using the open-source ML model (MLM) Extreme Gradient Boosting model (XGBoost) with minimal predictor variables, including age, sex, and AHA-PREVENT. The MLM was monotonically constrained to preserve known associations between risk factors and ASCVD risk. Along with sex, race and ethnicity data from the electronic health record were collected to validate the performance of ASCVD risk prediction in subgroups. Data were analyzed from August 2021 to February 2024. Consistent with the AHA-PREVENT model, ASCVD events were defined as the first occurrence of either nonfatal myocardial infarction, coronary artery disease, ischemic stroke, or cardiovascular death. Cardiovascular death was coded via government registries. Discrimination, calibration, and risk reclassification were assessed using the Harrell C index, a modified Hosmer-Lemeshow goodness-of-fit test and calibration curves, and reclassification tables, respectively. In the test set of 38 137 patients (mean [SD] age, 64.8 [6.9] years, 22 708 [59.5]% women and 15 429 [40.5%] men; 935 [2.5%] Asian, 2153 [5.6%] Black, 1414 [3.7%] Hispanic, 31 400 [82.3%] White, and 2235 [5.9%] other, including American Indian, multiple races, unspecified, and unrecorded, consolidated owing to small numbers), MLM-PREVENT had improved calibration (modified Hosmer-Lemeshow P > .05) compared to the AHA-PREVENT model across risk categories in the overall cohort (χ23 = 2.2; P = .53 vs χ23 > 16.3; P < .001) and sex subgroups (men: χ23 = 2.1; P = .55 vs χ23 > 16.3; P < .001; women: χ23 = 6.5; P = .09 vs. χ23 > 16.3; P < .001), while also surpassing a traditional recalibration approach. MLM-PREVENT maintained or improved AHA-PREVENT's calibration in Asian, Black, and White individuals. Both MLM-PREVENT and AHA-PREVENT performed equally well in discriminating risk (approximate ΔC index, ±0.01). Using a clinically significant 7.5% risk threshold, MLM-PREVENT reclassified a total of 11.5% of patients. We visualize the recalibration through MLM-PREVENT ASCVD risk charts that highlight preserved risk associations of the original AHA-PREVENT model. The interpretable ML approach presented in this article enhanced the accuracy of the AHA-PREVENT model when applied to a local population while still preserving the risk associations found by the original model. This method has the potential to recalibrate other established risk tools and is implementable in electronic health record systems for improved cardiovascular risk assessment.