Risk Of Cardiovascular Events Research Articles

The role of myocardial bridging in athletes with ST-segment depression or T-wave inversion on exercise testing

Abstract Background Myocardial bridging (MB) is a congenital anomaly in which a myocardial band partially or completely covers a coronary artery. It is a common finding in the general population, but it is more frequent in athletes. MB can cause ST-segment depression on exercise testing, which can be misinterpreted as coronary artery disease and generate the prohibition of sports. Aim To evaluate the presence of Myocardial Bridging (MB) through Multi-Slice Tomography Angiography in Moderate to High Intensity Athletes with Electrocardiographic changes and normal parietal motility in Stress Ultrasound with Exercise Methods This study included 159 athletes who had ST-segment depression or T-wave inversion on exercise testing. All participants underwent coronary angiography and/or multislice computed tomography coronary angiography. In addition, follow-up was 36 months (+/- 18 months) to assess the presence of major adverse cardiovascular events (MACE). Results A total of 3790 stress tests were requested from the Cardiology and Sports Clinic: 3631 (95.8%) were completely normal (no ST changes and normal parietal motility) and 159 (4.2%) showed ST segment depression. Of the 159 athletes, 42 (1.11%) had ST depression in the inferior and/or lateral segments and abnormal parietal motility at maximal exercise and were referred for invasive coronary angiography. The remaining 117 (3.09%) had the following ECG changes: 88 (72.21%) inferior and/or lateral ST segment depression and 29 (24.78%) T wave inversion without ST segment depression. Ninety-two (78.64%) of the above 117 athletes were diagnosed with 1 or more MBs in the coronary arteries. One hundred and forty-three MBs were found. The most common location was the anterior descending coronary artery (n=61; 42.6%) in its middle and distal third, followed by findings in the diagonal (n=30; 20.9%), circumflex (n=28; 19.5%) and marginal (n=24; 16.7%) branches. No MACE was recorded during the follow-up period and no further complex diagnostic studies were required. Conclusions Our study suggests that MB is a common cause of ST-segment depression and/or T-wave inversion on exercise testing in athletes. MB is usually benign and does not increase the risk of cardiovascular events. Therefore, athletes with MB should be allowed to continue participating in sports.ECG during maximal exercise stress echocTMSC of athlete

Modifiable risk factors and incident cardiovascular events in gout patients

Abstract Background Gout is associated with increased risks of cardiovascular events. However, it remains uncertain whether achieving the control targets for risk factors can attenuate this risk. This study evaluated the association between the attainment of targeted seven risk factors and the incidence of major adverse cardiovascular events (MACCE) among patients with gout. Methods From the UK Biobank database, we analyzed data from participants diagnosed with gout at baseline (2006-2010). These individuals were followed to monitor the incidence of MACCE. Gout patients were stratified based on the achievement of seven predefined risk factor targets at baseline: body mass index 18.5-24.9, adherence to a high-quality diet, engagement in regular exercise, non-smoking status, abstention from alcohol, hemoglobin A1c <48 mmol/mol, and serum urate < 360 μmol/L. The primary outcome was the incidence of MACCE, encompassing all-cause death, stroke, or myocardial infarction. Cox model was used to identify independent predictors of MACCE. Results After a median follow-up of 14.1 years, 1,318 of 6,273 gout patients developed MACCE. Among individuals with gout, the risk of MACCE decreased stepwise with the number of optimally managed modifiable risk factors. For participants exhibiting 1, 2, 3, and ≥4 optimal modifiable factors, the hazard ratios (HRs) were 0.39 (95% confidence interval (CI): 0.26-0.58), 0.30 (95%CI: 0.20-0.44), 0.28 (95%CI: 0.19-0.41), and 0.24 (95%CI: 0.16-0.36) respectively, showing a significant trend towards risk reduction (Ptrend <0.001). Conclusion Among individuals with gout, there is a stepwise decrease in the risk of MACCE with every additional risk factor that is optimally controlled.Study flowStratified analysis for adjusted HRs

Exercise stress testing recovery kinetics: the forgotten phase

Abstract Background Impaired exercise capacity is a cardinal feature of heart failure (HF). Peak oxygen uptake (pVO2) and ventilatory efficiency (VE/VCO2 slope) during exercise are well-consolidated prognostic markers in patients with HF. A previous study suggested that abnormally prolonged VO2 recovery, specifically the failure to decrease VO2 from peak exercise by 10.5 mL/kg/min at 180 seconds of the recovery phase, predicts adverse outcomes in HF. However, it is unknown to what extent the recovery of VEqCO2, a marker of ventilation/perfusion mismatch, adds prognostic value to the already existing parameters. Purpose The aim of this study was to characterize the functional and prognostic significance of VEqCO2 kinetics following peak exercise in individuals with HF. Methods This retrospective single-center study included consecutive adult patients with chronic (>3 months) and stable HF with left ventricular ejection fraction (LVEF) <50% who underwent cardiopulmonary exercise testing (CPET) between 2015 and 2020. Following maximal exercise, patients recovered over a 3-minute period (walking 2km/h for 1 minute and sittng passively for 2 minutes). VO2 and VEqCO2 kinetics during recovery, described as the absolute difference to peak VO2 (difVO2) and VEqCO2 (difVEqCO2), were measured at 30, 60, 120, and 180 seconds. Outcomes were assessed as a composite of cardiovascular (CV) death, urgent cardiac transplant, or left ventricular assist device (LVAD) implantation at 1 year. Results A total of 238 patients were included (mean age 58 ± 12 years; 82% males; mean LVEF 34 ± 10%; 68% with ischemic HF; 75% in NYHA class II-III; mean pVO2 18 ± 6 mL/kg/min; mean VE/VCO2 slope 41 ± 12). During the 1-year follow-up, 19 patients met the endpoint (8 CV deaths, 8 urgent heart transplants, and 3 LVAD). ROC curve analysis showed that the best correlation between difVEqCO2 and outcomes was apparent at difVEqCO2 of 180 seconds (AUC 0.83) with a cut-off value of 1 (sensitivity 93%, specificity 58%). These patients, who had a decrease in VEqCO2 (difVEqCO2 >1) at 180 seconds, were significantly older (p=0.02), had a lower LVEF (p<0.001), and higher NYHA (p<0.001). They were at an increased risk of cardiovascular events compared to those with an increase in VEqCO2 (difVEqCO2 <1) at 180 seconds (event-free survival at 1 year 86% vs. 98%, log-rank p<0.001). In multivariate analysis, the statistical association between difVEqCO2 and outcomes remained significant, even after adjusting for difVO2 at 180 seconds (HR 4.315, CI95% (1.349-13.804), p=0.014). Conclusion Abnormal VEqCO2 kinetics in the recovery period of CPET is an easily recognizable non-invasively derived measurement that predicts outcomes in HF. VEqCO2 may complement the evaluation of VO2 and other parameters during recovery to further improve prognostic risk stratification in HF.

Prognostic role of ECG patterns in Anderson Fabry disease

Abstract Background Anderson Fabry disease (AFD) is an X-linked lysosomal storage disorder leading to a deficiency in α-galactosidase A and globotriasylceramide (Gb3) deposition in different organs. Cardiac involvement is extremely common. It has been shown that the ECG abnormalities are directly correlated with the progressive accumulation of glycosphingolipids in the myocardium and cardiac conduction system. However, it is still unclear whether the ECG alterations are correlated with clinical events. Purpose To evaluate the prognostic role of ECG patterns in an unselected population of patients with AFD. Methods We conducted a retrospective multicenter study enrolling 215 consecutive patients. Based on the baseline ECG the study population was divided into the following five groups: 1) normal ECG or minimal alterations; 2) left ventricular hypertrophy (LVH) without signs of overload; 3) isolated negative T waves in the inferior and/or lateral leads; 4) LVH with signs of overload with or without incomplete right bundle branch block (RBBB); 5) complete RBBB. The primary endpoint was the composite of sudden cardiac death, resuscitated cardiac arrest, sustained ventricular tachycardia, and heart failure. Results Median age of study population was 45 years (32-57), and 86 patients (40%) were men. The rate of classic phenotype was 68%. Patients with ECG patterns 3 and 4 were older at baseline, more frequently affected by arterial hypertension, mostly male and showed greater left ventricular thickening, At a median follow up of 60 months (25-83) the overall Kaplan-Meier survival free from the primary endpoint was 57%: the Kaplan-Meier survival estimates of ECG groups were 66%, 75%, 68%, 27% e 52% respectively (log Rank 0.0026). On multivariable analysis patients belonging to either 3 or 4 group showed an increased risk of primary endpoint (HR= 2.45; 95% CI 1.04-5.78, p=0.040) compared to other groups. Conclusion ECG at baseline may be a useful tool to predict the risk of cardiovascular events in Anderson-Fabry Disease. Future studies should investigate if ECG may be useful also to evaluate the clinical response to specific therapy.

Pregnancy complications and long-term risk of cardiovascular events in women with heart disease

Abstract Background/Introduction Women with congenital heart or acquired heart disease are at increased risk of atherosclerotic cardiovascular disease. Pregnancy complications are established risk factors for cardiovascular disease in the general population, but their prognostic value for cardiovascular outcomes in the population with congenital or acquired heart disease is unknown. Purpose To determine the frequency and prognostic value of pregnancy complications for the risk of cardiovascular outcomes in women with congenital or acquired heart disease. Methods This nationwide registry-based cohort study included women in Sweden with heart disease (pulmonary arterial hypertension, congenital heart disease or acquired valvular heart disease) with singleton births registered in the national Medical Birth Register between 1973 and 2014. Exposures of pregnancy complications (preeclampsia/gestational hypertension, preterm birth or birth of an infant small for gestational age) were collected from the Medical Birth Register, and cardiovascular outcomes (mortality and hospitalizations) from the Cause of Death Register and the National Inpatient Register. Cox regression models were performed with time-dependent covariates, to determine the possible prognostic value of the studied pregnancy complications for cardiovascular outcomes including atherosclerotic cardiovascular disease, heart failure and arrythmias after adjustment for major confounding including smoking and body mass index. Results Among the total of 2,134,239 women included from the Medical Birth Register, 2,554 women with 5,568 singleton births were affected by heart disease. Preeclampsia/gestational hypertension affected 5.8% of pregnancies, preterm birth 9.7%, and birth of an infant small for gestational age 2.8%. Preterm birth (adjusted HR 1.91 (95% CI 1.38-2.64)) was associated with an increased risk of maternal all-cause mortality. Preeclampsia/gestational hypertension (adjusted HR 1.64 (95% CI 1.18-2.29)) and preterm birth (adjusted HR 1.56 (95% CI 1.19-2.04)) were associated with an increased risk of hospitalizations for atherosclerotic cardiovascular disease. Conclusions Pregnancy complications were frequent in women with congenital or acquired heart disease. With a median follow-up time of 22 years, preterm birth was associated with a higher risk of cardiovascular mortality, and preeclampsia/gestational hypertension and preterm birth were associated with cardiovascular morbidity. In women with heart disease, pregnancy complications may provide additional information for the risk assessment of future cardiovascular outcomes.Overview of study designPrevalence and risk estimation

The role of coronary artery calcium score and european score2 in primary prevention of cardiovascular disease

Abstract Background There is limited evidence about the role of using coronary artery calcium (CAC) score in conjunction with the European SCORE2 (systematic coronary risk evaluation) for the identification of individuals at higher risk of cardiovascular disease. Purpose To evaluate the relationship between CAC score and the European SCORE2 for cardiovascular risk stratification in an asymptomatic population in primary prevention. Methods This is a preliminary analysis from a single-centre, prospective, randomised 1:1, controlled trial assessing the use of CAC score vs standard preventive strategies in asymptomatic individuals undergoing primary cardiovascular prevention. The 10-year risk of cardiovascular events was assessed with either SCORE2 (ages 45-69) or SCORE2-OP (ages 70-89). Subjects were classified as 1) low to moderate risk, 2) high risk, and 3) very high risk according to SCORE2/SCORE2-OP. CAC score was assessed by ECG gated low-dose computed tomography with no contrast administration. A CAC score of zero was considered to reclassify risk one level downward in high or very-high risk patients. CAC score ≥ 100 was used to reclassify risk one level upward in patients with low to moderate risk and a CAC score > 1000 to reclassify risk upward in subjects with high risk. Results A total of 1,252 participants: 627 in the CAC group and 625 in the control group, median age 55 yrs, 25th-75th 50-61 yrs, with availability of SCORE2 and SCORE2-OP were included in this analysis. SCORE2/SCORE 2-OP was similar in the CAC and control groups. Among the subjects in the CAC group, there was a highly significant difference in SCORE2/SCORE 2-OP between participants with CAC score = zero and those with CAC > zero (median 5.6, 25th-75th 3.6-8.55 vs 2.9, 1.8-4.6, p< 0.001) as well as between those with CAC ≥ 100 and those with CAC score < 100 [median 6.8, 25th-75th (10.3-4.5) vs 3.3 (2.0-5.3), p<0.001]. The prevalence of CAC score = zero was 75% in the low to moderate risk group, 47% in the high risk, and 20% in the very high risk, p<0.001. By contrast the prevalence of CAC score ≥ 100 was 7% in the low to moderate risk group, 24% in the high risk, and 45% in the very high risk, p< 0.001. The proportion of patients classified as low to moderate risk group was 72% with CAC score vs 59% without CAC score, high risk 23% with CAC score vs 35% without CAC score, very high risk 5% vs 6% respectively, p<0.001. Using CAC score risk reclassification occurred in 48% downward and 2% upward in originally classified high risk subjects, 7% upward in originally classified low to moderate risk, and 20% downward in originally classified very high risk subjects. Conclusions CAC score may lead to risk reclassification in a substantial proportion of individuals, in particular among those originally classified as high risk by the SCORE2/SCORE2-OP. The cardiovascular risk prediction accuracy of adding CAC score to SCORE2/SCORE2-OP awaits validation at long-term follow-up.

Quality of life and clusters of patient characteristics in individuals with statin intolerance

Abstract Background Statin intolerance (SI) is associated with increased risk for cardiovascular events and mortality. The characteristics and symptoms of patients with SI are incompletely known. Methods The statin intolerance registry (SIR) is an observational, prospective, multicenter study that included n = 1111 patients between 2021 and 2023 in Germany. SI was defined as the inability to tolerate at least two different statins due to symptoms that resolved after statin-discontinuation. SIR baseline data were compared with the population-based LIFE-Adult-Study (n = 9983). Results The mean age was 66.1 years. Patients with SI had impaired quality of life with a mean EQ VAS score of 64.9 (SD 18.1) (Figure 1). The problems related to pain/discomfort (55.0%), mobility (32.3%), usual activity (23.9%), and anxiety/depression (20.4%). Diagnosis of depression was frequent (10.3%). 95.9% of patients with SI reported muscle symptoms that were associated with high severity of pain in 43.2% of patients. A higher percentage of SI patients was female in comparison to patients on statin in LIFE-Adult (57.6 vs. 38.2%). Women reported more depressive symptoms and lower quality of life in all domains compared to men. The symptoms increased with age. A data-driven k-means analysis based on variables predicting severity of pain while on statin therapy identified 5 clusters of SI patients (Figure 1). The clusters differed in sex, premature ASCVD, depression, quality of life, comorbidities, and expectations to tolerate statin therapy. Conclusion Overall, patients with SI have a highly impaired quality of life. Women are more frequently and more severely affected. The identified clusters may help identify patients at risk for SI and to develop individualized strategies to improve patient trajectories.

Genome-wide association study of CMR image-based aortic stiffness in 45,789 individuals identifies loci linked with cardiovascular diseases

Abstract Background The use of artificial intelligence on large-scale cardiac magnetic resonance (CMR) imaging data has enabled detailed characterisation of cardiac shape and function for use in genome-wide association studies (GWAS), leading to improved understanding of genetic aetiology of cardiovascular diseases (CVDs). Aortic stiffness is associated with increased risk of cardiovascular events in observational studies. Here, we present a novel CMR-based pressure-independent measure of aortic stiffness, identify genetic associations and explore links with CVDs. Purpose Identify genetic contributions to pressure-independent aortic stiffness and links to CVDs using large-scale GWAS analysis on the UK Biobank cohort. Methods A pre-trained neural network was used to segment CMR images of participants in the UK Biobank to quantify ascending aorta diameter, which together with contemporaneous systolic and diastolic blood pressure measurements (SBP, DBP, respectively) were used to calculate a pressure-independent measure of aortic stiffness (β0). The measurement assumes an exponential relationship between pressure and aortic diameter. We then performed a GWAS on β0 in 45,789 participants of European ancestry without CVDs. A multi-trait-based conditional & joint analysis (mtCOJO) was performed to estimate genetic effects independent of SBP, DBP and aortic area. We mapped the independent lead variants associated with aortic stiffness at P < 5x10-8 to nearest gene, and characterised shared genetic association across CVDs using Open Targets Platform database. Results The GWAS identified 17 independent lead variants, including 6 that remained significant in the conditional analysis. Four of these lead variants, not previously reported in GWAS of other aortic traits, were located near CTD-2203A3.1, MCF2L, CFDP1 and CDH13 genes (red annotations in the Figure). MCF2L, CFDP1 and CDH13 have been associated with coronary artery disease, and CFDP1 with myocardial infarction and coronary atherosclerosis in previous studies. Conclusion A GWAS of CMR-derived aortic stiffness identified 4 loci distinct from other aortic traits that also associate with other CVDs, suggesting genetic links between aortic stiffness and CVDs. Further analyses are required to explore biological mechanisms underlying these genetic associations.Aortic Stiffness Manhattan Plot

Remnant cholesterol and mortality in 37.559 patients from LIPIDOGRAM 2004, 2006 and 2015 studies

Abstract Introduction Remnant cholesterol (remnant-C) is produced by metabolism of triglyceride rich proteins and contributes to residual cardiovascular (CVD) risk. Purpose To asses association between remnant cholesterol and all-cause mortality in a large cohort of patients under the care primary care physicians. Methods The LIPIDOGRAM studies were carried out in the primary care in Poland in 2004, 2006 and 2015. Patients (n=47,398) recruited in all 16 administrative regions in Poland and physicians were proportionally distributed to the number of inhabitants in each administrative region. Each patient was asked to fill the questionnaire on risk factors, chronic diseases, treatment, and lifestyle. In the present analysis we included consecutive patients with body mass index (BMI) >18.5 kg/m2 aged 18-70 years. Median follow up was (5.3 years (interquartile range 5.7-17.3). For this analysis we approved the cut-off point of fasting remnant cholesterol >30 mg/dL (>0.77 mmol/L) that differentiated subjects at high risk of cardiovascular events. We used univariate and multivariate Cox regression modelling to assess the association between remnant-C and all-cause mortality. Results Finally, 37,559 patients were included meeting the inclusion criteria and for which the follow-up data was available. Mean remnant-C concentration was: 27 mg/dl / 0.7 mmol/l (standard deviation 15 mg/dl/ 0.38 mmol/l). Remnant-C was associated with 5-year mortality and overall mortality during the study period, with hazard ratios (HR) of 1.21 (95% CI: 1.04-1.41, p<0.001) and 1.42 (95% CI: 1.32-1.53, p<0.001) for each 1 mmol/l increase, respectively. After adjusting for age, sex, BMI, education level, place of residence, hypertension, diabetes mellitus, smoking, previous myocardial infarction, metabolic syndrome presence, and statin and fibrate treatments, remnant-C was associated with long-term mortality—HR (per 1 mmol/l) of 1.08 (95% CI: 1.00-1.17, p=0.049)—but not with 5-year mortality—HR (per 1 mmol/l) of 0.97 (95% CI: 0.83-1.13, p=0.7). Predefined level of remnant-C > 30 mg/dl (0.77 mmol/l) was associated with higher 5 year (HR- 1.15, 95%CI (1.02-1.31, p=0.021) (Figure 1A) and long-term all-cause mortality (HR- 1.26, 95%CI (1.19-1.33, p<0.001) (Figure 1B). Conclusions Higher remnant-C cholesterol levels are associated with long term all-cause mortality in patients aged 18-70 years.

Bidirectional relationship between kidney disease progression and cardiovascular events in type 2 diabetes: new Insights from the CANVAS Program and CREDENCE trial

Abstract Background The extent to which chronic kidney disease (CKD) progression increases cardiovascular risk, and whether different types of cardiovascular events affect risk of CKD progression, is incompletely understood. Purpose We sought to explore risk of cardiovascular events before and after CKD progression, and CKD progression before and after different cardiovascular events in patients with type 2 diabetes. Methods We conducted a pooled individual participant data analysis of the CANVAS Program and CREDENCE trial. Using Poisson regression, we assessed the incidence of major adverse cardiovascular events ([MACE] stroke, myocardial infarction, or cardiovascular death) and hospitalised heart failure (HHF) or cardiovascular death before and after CKD progression (defined as 40% decline in estimated glomerular filtration rate [eGFR] or kidney failure), and CKD progression before and after nonfatal cardiovascular events, with no adjustment for confounding related to subgroups defined by post-randomization variables. We estimated the cumulative incidence of all-cause mortality after different nonfatal cardiovascular and kidney outcomes, including different thresholds of CKD progression (kidney failure, 40% or 50% decline in eGFR or doubling of serum creatine) using Cox regression models. Results Among 14,464 participants (mean age 63.7 years, 35.3% female, mean eGFR 55mL/min/1.73m2 and median urinary albumin:creatinine ratio 34mg/g) over a median follow-up of 2.5 years, 1,482, 1,076 and 1,020 experienced MACE, HHF or cardiovascular death, and CKD progression, respectively. After (vs. before) CKD progression, there was an approximate 3-fold increase in incidence of MACE (30.2 vs. 93.8 per 1000-patient-years) and 4-fold increase in HHF or cardiovascular death (21.0 vs. 79.3 per 1000-patient-years). Conversely, the incidence of CKD progression was approximately 1.5-fold higher after (vs. before) nonfatal myocardial infarction or stroke (21.7 vs. 34.1 per 1000-patient-years) and 5-fold higher after HHF (21.2 vs. 108.2 per 1000-patient-years). These patterns were consistent in both treatment arms, with unadjusted incidence rates for clinical events appearing numerically lower in canagliflozin compared to placebo-treated participants (Figure 1). Of all non-fatal cardio-kidney outcomes, HHF and doubling of serum creatine or kidney failure conferred the highest risk of death (Figure 2). Conclusion Atherosclerotic and heart failure risk increases substantially after CKD progression. CKD progression was accelerated after cardiovascular events, particularly HHF. Treatment with canagliflozin was associated with lower event rates before and after a serious cardio-kidney outcome, suggesting continued use of canagliflozin may be beneficial even after cardiovascular events and CKD progression.Figure 1.Figure 2.

Neutrophil-to-lymphocyte ratio can predict the clinical prognosis of patients with primary adosteronism

Abstract Background Excess aldosterone-mediated inflammatory response is thought to be a factor in the high risk of cardiovascular events in patients with primary aldosteronism (PA). Leucocyte related inflammatory parameters, especially NLR, were significantly independent of aldosterone (PAC) in PA patients. However, the impact of NLR on the long-term prognosis of PA patients is unclear. Objective To explore the predictive value of neutrophil-to-lymphocyte ratio (NLR) on the long-term prognosis of patients with primary aldosteronism (PA). Methods The data for this study were derived from the Tianjin Health and Medical Big Data Super platform, comprising a retrospective cohort of patients discharged from 72 hospitals in our city from 2010 to 2023. According to the inclusion and exclusion criteria, 570 patients were ultimately included in the statistical analysis. Each patient had laboratory measurements, including blood cell counts, taken after admission and before interventional treatment. The primary endpoint was major cardiovascular events (MACEs), defined as cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke. Results During a mean follow-up period of 5 years, 125（21.9%）MACEs were recorded. ROC curve analysis displayed that the best cut-off value of NLR for predicting MACEs was 4.87. The MACEs of the high NLR group at 1 year, 3 years, and 5 years were higher than those of the low NLR group（25.0% vs 9.4%，40.3% vs17.1% 和 40.3% vs 19.3%；P＜0.05).Kaplan-Meier survival curve analysis showed that the survival rate of the low NLR group was higher than that of the high NLR group (P<0.001). The results of multivariate Cox proportional hazards regression analysis showed that NLR was an independent risk factor affecting the prognosis of PA patients, and the difference was statistically significant (P<0.05). Conclusions Elevated NLR is associated with adverse prognosis in patients with PA. NLR can serve as a simple and practical indicator to evaluate the long-term prognosis of PA patients. These findings warrant external validation, preferably in a prospective design.

Body mass index as a contributor to the accumulation of lipidic plaque materials in statin-treated type 2 diabetic patients with coronary artery disease: sub-analysis from the OPTIMAL randomized study

Abstract Background Patients with type 2 diabetes mellitus more likely exhibit obesity. Pathophysiologically, obesity promotes a range of metabolic disturbances including insulin resistance, dyslipidemia and hypertension, in addition to the secretion of adipokines and pro-inflammatory cytokines from excessive fat accumulation. These atherogenic features may promote instability of atherosclerotic plaques, which ultimately result in elevating a risk of atherosclerotic cardiovascular disease. However, it remains to be fully elucidated how obesity affects atherosclerotic plaque features in type 2 diabetic patients with coronary artery disease (CAD). Near-infrared spectroscopy (NIRS) imaging enables to quantitatively visualize lipidic plaque materials in vivo. This imaging modality provides insights into lipidic plaque features in obese patients with type 2 diabetes mellitus. Purpose To elucidate the association of body mass index (BMI, kg/m2) with lipidic plaque materials in type 2 diabetic patients. Methods The OPTIMAL study was a prospective randomized controlled trial to evaluate the efficacy of continuous glucose monitoring (CGM) guided glycemic control on coronary atherosclerosis in statin-treated type 2 diabetic participants with CAD requiring PCI. 94 patients were randomized into CGM-guided or HbA1c-guided glycemic control. Serial NIRS imaging was conducted to monitor non-culprit lesions at baseline and week 48. The current sub-analysis included 78 patients with both baseline BMI data and evaluable baseline NIRS/IVUS images. Results All of study subjects received a statin (high-intensity statin use=36%), and the averaged LDL-C level was 86.7±26.3 mg/dL. The average BMI and HbA1c level were 24.7±3.1 kg/m2 and 7.5±0.9%, respectively (Table 1). On NIRS imaging analysis, maxLCBI4mm at non-culprit lesions was 286.2±167.0, and 21.8% of study subjects exhibited maxLCBI4mm >400 (Table 2). BMI was associated with maxLCBI4mm (p<0.001). Multivariate analysis adjusting clinical characteristics and LDL-C demonstrated that BMI was an independent contributor to maxLCBI4mm [estimate=17.15 (12.88-21.42), p<0.001] (Table 2). Even in patients receiving high-intensity statin, BMI was still associated with maxLCBI4mm (p<0.001). Conclusions A greater accumulation of lipidic plaque materials was observed in association with BMI in statin-treated type 2 diabetic patients with CAD. This presence of enhanced plaque vulnerability at non-culprit lesions, in the setting of obesity, may contribute to an increased risk of cardiovascular events in type 2 diabetic patients with CAD. The current finding suggests the need to adopt further therapeutic approaches to favourably modify plaque vulnerability in type 2 diabetic patients exhibiting obesity.Table 1:Clinical DemographicsTable 2:Factors Associated with maxLCBI

Remnant cholesterol, clinical characteristics and mortality in 41.767 patients from LIPIDOGRAM 2004-2015 studies - the factor analysis for mixed data cluster analysis

Abstract Introduction Remnant cholesterol (remnant-C) contributes to residual cardiovascular risk and is produced by metabolism of triglyceride rich proteins. Aim To assess association between clinical characteristics of patients with elevated remnant-C in a large cohort of patients under the care of primary care physicians. Methods The LIPIDOGRAM studies were carried out in the primary care in Poland in 2004, 2006 and 2015. Patients (n=47,398) recruited in all 16 administrative regions in Poland and physicians were proportionally distributed to the number of inhabitants in each administrative region. Each patient was asked to fill the questionnaire on risk factors, chronic diseases, treatment and lifestyle. In the present analysis we included patients with body mass index (BMI )>18.5 kg/m2 aged 18-75 years. We set the cut-off point of fasting remnant cholesterol at >30 mg/dL (>0.77 mmol/L) that differentiated subjects at high risk of cardiovascular events. We carried out Factor Analysis for Mixed Data (FAMD) cluster analysis to discern groups of patients with similar clinical profiles. Results 41,767 patients, for which we had all relevant data, were included in the analysis. Follow-up rate was 97.8%. Three FAMD-derived clinical characteristics patterns accounted for 47.8% of the total variance and were retained for further analysis. The first pattern was associated with higher prevalence of metabolic syndrome (MetS), higher waist circumference, higher levels of non-HDL-C and remnant-C levels. The second pattern was distinguished by lipid parameters, particularly higher HDL-C levels, and was not significantly associated with comorbid conditions. The third pattern was linked to male sex, previous myocardial infarction, smoking, age, lower remnant-C levels, and reduced prevalence of obesity. All patterns were associated with 5-year mortality. The hazard ratio (HR) for mortality per 1 standard deviation (SD) increase in the first pattern score was 1.18 (95% CI: 1.16-1.22, p<0.001). Patients with clinical characteristics corresponding to second pattern had more favorable outcome HR (per 1SD score increase) – 0.75, 95%CI (0.73-0.78, p<0.001). Patients in third cluster, similarly to patients in cluster 1 had increased mortality HR (per 1SD score) – 1.10, (95%CI:1.06-1.15, p <0.001). Higher (>0.77 mmol/l / 30 mg/dl) remnant-C cholesterol significantly contributed to classification of patients into first and third clusters. It was positively associated with first pattern (r=0.64, p<0.001), but negatively with the third pattern (r=0.39, p<0.001). Conclusions Elevated Remnant-C was associated with clinical pattern typical for metabolic syndrome. Interestingly, lower remnant-C levels in patients with comorbidities and more advanced age may not automatically be indicative of a better prognosis – this requires further investigation.Figure 1.Figure 2.

Effect of pre-procedural blood pressure on one-year cardiovascular events after percutaneous coronary intervention in patients with acute myocardial infarction

Abstract Background Although high systolic blood pressure (SBP) and low diastolic blood pressure (DBP) are associated with adverse cardiovascular outcomes in coronary artery disease, their impact on patients with acute myocardial infarction (AMI) remains unclear. Methods This multicenter prospective study included 874 AMI patients undergoing percutaneous coronary intervention (PCI) with pre-procedural blood pressure recorded. Patients with cardiogenic shock and missing blood pressure data were excluded. The patients were categorized based on SBP (high ≥120 mmHg, low <120 mmHg) and DBP (high ≥70, low <70 mmHg) into four groups: high SBP and high DBP (HSHD), high SBP and low DBP (HSLD), low SBP and high DBP (LSHD), and low SBP and low DBP (LSLD) group. The primary endpoint was a composite of all-cause mortality, myocardial infarction, stroke, and major bleeding. Results The average age of the patients was 68.9 years, with a mean pulse pressure of 58 ± 19 mmHg. The Kaplan-Meier curves showed significant differences in the primary endpoints among the four groups (Log-rank test, p <0.001). At 12 months, the primary endpoint occurrence was highest in the HSLD group (13.3%) and lowest in the LSHD group (2.4%). Additionally, multivariate Cox regression analysis revealed that the HSLD group, compared to the HSHD group, was independently correlated with an increased risk of cardiovascular events (hazard ratio 2.43, 95% confidence interval 1.16-5.11; p = 0.019). Conclusion Pre-procedural HSLD serves as an independent predictor and is associated with one-year adverse cardiovascular outcomes in AMI patients.Patient diagramKaplan-Meier one-year outcome

The potential effects of methotrexate on cardiovascular outcomes in rheumatoid arthritis patients: a multi-institutional analysis

Abstract Introduction and Purpose The association between rheumatoid arthritis (RA) and increased risk of developing cardiovascular disease has been previously described. Recent studies have also shown that methotrexate may reduce the risk of cardiovascular events in patients with RA but have been limited by small sample size and/or demographic constraints. Methotrexate is a first-line drug treatment for RA and works by suppressing multiple anti-inflammatory and immune reactions, thereby reducing the inflammation that promotes progression of cardiovascular disease in these patients. The goal of this study is to evaluate the potential benefit of methotrexate use on cardiovascular outcomes in patients with RA on a larger scale by utilizing a large international medical record database. Methods The TriNetX Diamond network was used for this study. Two cohorts were generated for comparison by using International Classification of Disease 10 (ICD-10) codes. Both cohorts included adult patients with a diagnosis of rheumatoid arthritis (M06) and both were excluded from being treated with the following biologic therapies: etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol. One cohort was on active treatment with methotrexate while the other was excluded from being on it. The cohorts were then balanced for age, gender, race, ethnicity, presence of known coronary artery disease (I20-I25) and history of prior cardiovascular diseases (Z86.7) by propensity score matching and use of the greedy nearest neighbor algorithm. This resulted in 471,054 patients in each arm. They were then compared for the outcomes of acute myocardial infarction, chronic ischemic heart disease, congestive heart failure, and death at 5 years. Results Untreated RA patients were 11% more likely to develop myocardial infarction (RR 1.11, 95% CI (1.09,1.14), P value <0.0001) and 14% more likely to develop chronic ischemic heart disease (RR 1.14, 95% CI (1.13,1.15), P value <0.0001). CHF incidence was 21% higher (RR 1.21, 95% CI (1.19,1.22), P value <0.0001) in the untreated group, but 5-year mortality in the two groups was comparable at around 8.2% (RR 0.98, 95% CI (0.97,0.997), P value 0.016). Conclusion This study confirms that methotrexate is associated with fewer cardiovascular events in RA patients, especially congestive heart failure. Although the use of methotrexate in patients with RA did not result in a mortality benefit, treatment may offer substantial improvements in patient morbidity and healthcare system cost. These benefits were seen in a sample of greater than 900,000 patients representing every adult demographic. These data reaffirm the previously described association between RA and cardiovascular disease and support the initiation of treatment with methotrexate for any adult patient with RA. Watchful waiting is associated with a higher incidence of adverse events in this population.

Prognostic significance of coronary flow velocity reserve in patients with peripheral arterial disease

Abstract Background Patients with lower extremity peripheral arterial disease (PAD) have a higher risk of cardiovascular events. Stress echocardiography (SE) based on regional wall motion abnormality (RWMA) is imperfect for risk stratification in PAD, but it can be complemented with an assessment of coronary flow velocity reserve (CFVR) in the mid-distal left anterior descending coronary artery. Purpose To assess the value of SE with RWMA and CFVR to predict survival in PAD. Methods In a retrospective analysis of prospectively acquired data in an observational, multicenter study, we recruited 359 patients (age 69±8 years, 240 [67%] males) with PAD referred for dipyridamole SE in 3 accredited laboratories. We assessed RWMA and CFVR (abnormal value <2.0). All patients were followed up for a median of 4.7 (interquartile range: 2.0 to 8.2 years). All-cause death was the outcome end-point. Results The positivity rate was 37/359 (10%) for RWMA and 159/359 (44%) for CFVR. During follow-up, 97 (27%) deaths were registered. At multivariable analysis, inducible RWMA and/or CFVR <2.0 (HR 2.58, 95% CI 1.65-4.04; p<0.0001), age ≥70 years, diabetes, dialysis treatment, and ejection fraction ≤50% were associated with decreased survival. The annual mortality was 7.4% in patients with RWMA and/or CFVR <2.0 and 2.7% in those with no RWMA and CFVR >2.0 (Figure, p<0.0001). Conclusion In patients with PAD, SE shows more than 4-fold higher prevalence of abnormal CFVR compared to RWMA. The prognostic value of CFVR outperforms RWMA, showing the importance of coronary microvascular dysfunction and diffuse, subcritical coronary atherosclerosis in determining the outcome.

Inclisiran-containing low-density lipoprotein cholesterol reduction effectively stabilizes atherosclerotic plaques

Abstract Background/Introduction Near-infrared spectroscopy (NIRS) allows to quantify lipid composition of coronary artery lesions. High plaque lipid content has been associated with increased adverse cardiovascular event risk. Purpose Aim of this study was to evaluate atherosclerotic plaque lipid content reduction in association with low-density lipoprotein (LDL-C) lowering on the background of intensive hypolipidaemic therapy. Methods NIRS investigation was performed in stable coronary artery disease patients having 20-50% stenosis in the proximal or middle third of a coronary artery. Segment of interest was repeatedly evaluated after 15 months. Lipid-rich plaques (LRPs) were defined as lesions with maximum lipid-core burden index within 4 mm (maxLCBI4 mm) >250. Study participants were taking high-intensity statin (atorvastatin 40 or 80 mg and rosuvastatin 20 or 40 mg) with or without ezetimibe for a run-in period of 4-6 weeks. Afterwards, in patients not achieving LDL-C level <1.8 mmol/l, add-on inclisiran was started. Baseline LDL-C was defined as the level at the time of initiation of optimal lipid-lowering therapy. Statistical significance level of 0.05 was set. Results Data of 36 patients was analyzed. Mean baseline maxLCBI4 mm was 203.9, reduced by 39.8% (-81.1, 95%CI -129.2 to -33.0) at 15-month follow-up (P=0.003). In 15 patients LRPs were detected with mean baseline maxLCBI4 mm 363.5, which was decreased by 35.8% (-130.3, 95%CI -235.0 to -25.7) (P=0.020). Mean LDL-C level at baseline was 2.5 mmol/l among all participants, lowered by 32.0% (-0.8, 95%CI -1.1 to -0.5) after 15 months of treatment (P<0.001). 19 patients received inclisiran in addition to high-dose statin and optional ezetimibe therapy. In 24 patients achieving LDL-C target <1.8 mmol/l at 15-month follow-up, a significant maxLCBI4 mm reduction from 208.5 by 48.4% (-101.0, 95%CI -169.3 to -32.7) was established (P=0.010). Among those having LDL-C >1.8 mmol/l, maxLCBI4 mm reduction from 194.7 by 21.2% (-41.25, 95%CI -94.7 to 12.2) was observed, however the change was not statistically significant (P=0.114). Conclusion LDL-C lowering with high-intensity hypolipidaemic therapy, including escalation to proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition, demonstrated atherosclerotic plaque stabilization by NIRS-detected lipid content decrease.

Remnant cholesterol predicts major cardiovascular events in coronary artery disease patients with NAFLD

Abstract Remnant cholesterol has attracted interest as a marker of cardiovascular event risk. The power of remnant cholesterol to predict major cardiovascular events (MACE) in patients with non-alcoholic fatty liver disease (NAFLD) is unclear and is addressed in the present study. We enrolled a high-risk cohort of 913 patients with coronary artery disease (CAD). NAFLD was diagnosed using the validated fatty liver index (FLI). Prospectively, MACE including cardiovascular death, non-fatal myocardial infarction and non-fatal stroke were recorded over a mean follow-up period of 9.5±5.2 years. At baseline, remnant cholesterol was significantly higher in patients with NAFLD (n=419) than in patients who did not have NAFLD (30±28 mg/dl vs. 18±17 mg/dl; p<0.001). During follow-up, 379 of our patients suffered MACE. Remnant cholesterol in Cox regression models adjusting for age, sex, hypertension, smoking, diabetes mellitus, body mass index and LDL cholesterol independently predicted MACE in the total study population (standardized adjusted HR 1.18 [1.08-1.30], p<0.001), and both in patients with NAFLD as well as in those who did not have NAFLD (standardized adjusted HRs 1.19 [1.05-1.35], p=0.006 and 1.24 [1.03-1.49], p=0.023, respectively). From our data we conclude that remnant cholesterol is a predictor of MACE in patients with CAD with and without NAFLD.

Long-term outcomes and operators' experience in primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.

Primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI) is typically performed by experienced operators. Therefore, the safety of pPCI for STEMI performed by less experienced operators with the support of experienced operators remains unknown. We aimed to investigate the long-term outcomes of pPCI for STEMI performed by less experienced operators with the support of experienced operators. In total, 775 STEMI patients were enrolled and divided into groups according to operator experience in PCI: less experienced (n = 384) and experienced (n = 391) operator groups. Experienced operators were defined as those who had performed > 50 elective PCI procedures per year as the first operator or instructional assistant, whereas less experienced operators were defined as others. When less experienced operators performed the pPCI, experienced operators supported them. The primary endpoint was any cardiovascular event, defined as a composite of cardiovascular death, nonfatal myocardial infarction, and unplanned hospitalization for heart failure. In the propensity score-matched analysis, 324 patients were included in each group. The cumulative incidence of the primary endpoint over a median of 5years in the less experienced operator group was similar to that in the experienced operator group (15% vs. 18%, P = 0.209). In the multivariate Cox proportional hazards model, there was no excess risk for patients operated upon by less experienced operators for the primary endpoint (adjusted hazard ratio, 0.85; 95% confidence interval, 0.58-1.25; P = 0.417). pPCI for STEMI by less experienced operators did not increase the risk of in-hospital mortality or 5-year long-term cardiovascular events if supported by experienced operators.

Influence of Diabetes Mellitus on Postoperative Complications After Total Knee Arthroplasty: A Systematic Review and Meta-Analysis

Background and Objectives: Total knee arthroplasty (TKA) is an effective treatment option for severe knee osteoarthritis. Understanding the impact of diabetes mellitus (DM) on postoperative outcomes is crucial for improving patient satisfaction after TKA. This study aimed to investigate the influence of DM on postoperative complications and mortality after TKA. Materials and Methods: We conducted a systematic review and meta-analysis by searching relevant studies published before December 2023 in the PubMed, EMBASE, Cochrane Library, Medline, and Web of Science databases. The assessment included demographic data, comorbidities, and postoperative complications after primary TKA for both DM and non-DM patients. The odds ratio (OR) was used to represent the estimate of risk of a specific outcome. Results: Thirty-nine studies were finally included in this meta-analysis. Patients with DM had higher rates of periprosthetic joint infection (OR: 1.71, 95% confidence interval [CI]: 1.46–2.00, p < 0.01) and prosthesis revision (OR: 1.37, 95% CI: 1.23–1.52, p < 0.01). Moreover, patients with DM showed an elevated incidence of pneumonia (OR: 1.54, 95% CI: 1.15–2.07, p < 0.01), urinary tract infection (OR: 1.86, 95% CI: 1.07–3.26, p = 0.02), and sepsis (OR: 1.61, 95% CI: 1.46–1.78, p < 0.01). Additionally, the postoperative risk of cardiovascular (OR: 2.49, 95% CI: 1.50–4.17, p < 0.01) and cerebrovascular (OR: 2.38, 95% CI: 1.48–3.81, p < 0.01) events was notably higher in patients with DM. The presence of DM increased the risk of deep vein thrombosis (OR: 1.58, 95% CI: 1.22–2.04, p < 0.01), but did not lead to an increased risk of pulmonary embolism. Most importantly, DM was associated with a higher mortality rate within 30 days after TKA (OR: 1.27, 95% CI: 1.02–1.60, p = 0.03). Conclusions: Patients with DM exhibited a higher rate of postoperative complications after TKA, and DM was associated with a higher mortality rate within 30 days after TKA. It is crucial to educate patients about the perioperative risk and develop evidence-based guidelines to prevent complications after TKA.