ABSTRACT The importance of macrophage polarization through atherogenesis is established. However, most studies rely on immunohistological approaches, which have several limitations, such as precluding comprehensive phenotypic analysis. The aim of this study was to perform an alternative analysis of macrophage phenotypes in advanced human atherosclerotic plaques and compare them with their presence in non‐atherosclerotic arteries. Atherosclerotic plaques from 70 individuals indicated for carotid endarterectomy, and samples of non‐atherosclerotic arterial tissue (renal artery, control group) from 45 living kidney donors were processed to obtain immunocytes and incubated with antibodies (CD45, CD14, CD16, CD36, CD163, and CD206) to be analyzed by flow cytometry. Macrophages in the atherosclerotic plaques tend to express CD16 more intensively than in non‐atherosclerotic arterial tissue (transient, CD16low p < 0.001, pro‐inflammatory, CD16high p < 0.001), and the expression is more closely associated with CD36 expression. Both transient and pro‐inflammatory macrophages are linked with the CD206−CD163+ or CD206+CD163+ phenotype in atherosclerotic plaques, while CD206−CD163− dominates within the anti‐inflammatory (CD16neg) population in the control group. Interestingly, when evaluating all macrophages (regardless of CD16 expression), almost all are CD163+ in both groups, supporting the critical importance of using a combination of specific markers. Our results provide a deeper insight into macrophage subpopulations in advanced human atherosclerotic plaques compared with those in non‐atherosclerotic vessels. Additionally, our data highlight the critical importance of using appropriate techniques, such as flow cytometry, allowing for simultaneous analysis of multiple markers to accurately and comprehensively characterize macrophages within the atherosclerotic plaque.

Carotid artery stenosis carries not only risk for ischemic strokes but also for other fatal cardiovascular events. Therefore, the control of modifiable cardiovascular risk factors as smoking, dyslipidemia, hypertension and diabetes mellitus is of primary importance in patients with carotid stenosis irrespectively of symptoms. This strategy is based on combination of lifestyle measures with pharmacotherapy. The basic lifestyle rule is expressed by the numbers 0-5-30; which mean 0 cigarettes, 5 portions of vegetables and fruits per day and 30 minutes of exercise per day. Very low concentrations of atherogenic LDL cholesterol (in patients at the highest risk less than 1.4 mmol/L) are to be reached; it is recently achievable by wide spectrum of potent hypolipemic drugs. In hypertension, the optimal levels of systolic blood pressure are 130-140 mmHg; in severe bilateral carotid stenoses slower lowering of blood pressure is recommended. Similarly, in diabetic individuals, hypoglycemia should be avoided caused by too intensive anti-diabetic treatment. Nevertheless, recently available antidiabetic drugs are less dangerous in this respect. Other risk factors recently under scrutiny are lipoprotein(a) and subclinical inflammation. Finally, very frequent but often critical and neglected risk factor is nonadherence of patients to cardiovascular risk management.

Background Heart failure is a common complication after myocardial infarction (MI) and is associated with increased mortality. Whether remote heart failure symptoms assessment after MI can improve risk stratification is unknown. The authors evaluated the association of the 23‐item Kansas City Cardiomyopathy Questionnaire (KCCQ) with all‐cause mortality after MI. Methods and Results Prospectively collected data from consecutive patients hospitalized for MI at a large tertiary heart center between June 2017 and September 2022 were used. Patients remotely completed the KCCQ 1 month after discharge. A total of 1135 (aged 64±12 years, 26.7% women) of 1721 eligible patients completed the KCCQ. Ranges of KCCQ scores revealed that 30 (2.6%), 114 (10.0%), 274 (24.1%), and 717 (63.2%) had scores <25, 25 to 49, 50 to 74, and ≥75, respectively. During a mean follow‐up of 46 months (interquartile range, 29–61), 146 (12.9%) died. In a fully adjusted analysis, KCCQ scores <50 were independently associated with mortality (hazard ratio [HR], 6.05 for KCCQ <25, HR, 2.66 for KCCQ 25–49 versus KCCQ ≥50; both P<0.001). Adding the 30‐day KCCQ to clinical risk factors improved risk stratification: change in area under the curve of 2.6 (95% CI, 0.3–5.0), Brier score of −0.6 (95% CI, −1.0 to −0.2), and net reclassification improvement of 0.71 (95% CI, 0.45–1.04). KCCQ items most strongly associated with mortality were walking impairment, leg swelling, and change in symptoms. Conclusions Remote evaluation of heart failure symptoms using the KCCQ among patients recently discharged for MI identifies patients at risk for mortality. Whether closer follow‐up and targeted therapy can reduce mortality in high‐risk patients warrants further study.

Abstract Background The highest mortality and morbidity worldwide is associated with atherosclerotic cardiovascular disease (ASCVD), which has in background both environmental and genetic risk factors. Apolipoprotein L1 (APOL1) variability influences the risk of ASCVD in Africans, but little is known about the APOL1 and ASCVD in other ethnic groups. Methods To investigate the role of APOL1 and ASCVD, we have genotyped four (rs13056427, rs136147, rs10854688 and rs9610473) APOL1 polymorphisms in a group of 1541 male patients with acute coronary syndrome (ACS) and 1338 male controls. Results Individual APOL1 polymorphisms were not associated with traditional CVD risk factors such as smoking, hypertension or diabetes prevalence, with BMI values or plasma lipid levels. Neither individual polymorphisms nor haplotypes were associated with an increased risk of ACS nor did they predict total or cardiovascular mortality over the 10.2 ± 3.9 years of follow‐up. Conclusions We conclude that APOL1 genetic variability has no major effect on risk of ACS in Caucasians.

AIMS:While heart failure (HF) symptoms are associated with adverse prognosis after myocardial infarction (MI), they are not routinely used for patients' stratification. The primary objective of this study was to develop and validate a score to predict mortality risk after MI, combining remotely recorded HF symptoms and clinical risk factors, and to compare it against the guideline-recommended Global Registry of Acute Coronary Events (GRACE) score. METHODS AND RESULTS:A cohort study design using prospectively collected data from consecutive patients hospitalized for MI at a large tertiary heart centre between June 2017 and September 2022 was used. Data from 1135 patients (aged 64 ± 12 years, 26.7% women), were split into derivation (70%) and validation cohort (30%). Components of the 23-item Kansas City Cardiomyopathy Questionnaire and clinical variables were used as possible predictors. The best model included the following variables: age, HF history, admission creatinine and heart rate, ejection fraction at hospital discharge, and HF symptoms 1 month after discharge including walking impairment, leg swelling, and change in HF symptoms. Based on these variables, the PragueMi score was developed. In the validation cohort, the PragueMi score showed superior discrimination to the GRACE score for 6 months [the area under the receiver operating curve (AUC) 90.1, 95% confidence interval (CI) 81.8-98.4 vs. 77.4, 95% CI 62.2-92.5, P = 0.04) and 1-year risk prediction (AUC 89.7, 95% CI 83.5-96.0 vs. 76.2, 95% CI 64.7-87.7, P = 0.004). CONCLUSION:The PragueMi score combining HF symptoms and clinical variables performs better than the currently recommended GRACE score.

Background Despite a general decline in mean levels across populations, LDL-cholesterol levels remain a major risk factor for acute coronary syndrome (ACS). The APOB , LDL-R , CILP , and SORT-1 genes have been shown to contain variants that have significant effects on plasma cholesterol levels. Methods and results We examined polymorphisms within these genes in 1191 controls and 929 patients with ACS. Only rs646776 within SORT-1 was significantly associated with a risk of ACS (P < 0.05, AA vs. + G comparison; OR 1.21; 95% CI 1.01–1.45). With regard to genetic risk score (GRS), the presence of at least 7 alleles associated with elevated cholesterol levels was connected with increased risk (P < 0.01) of ACS (OR 1.26; 95% CI 1.06–1.52). Neither total mortality nor CVD mortality in ACS subjects (follow up—9.84 ± 3.82 years) was associated with the SNPs analysed or cholesterol-associated GRS. Conclusions We conclude that, based on only a few potent SNPs known to affect plasma cholesterol, GRS has the potential to predict ACS risk, but not ACS associated mortality.

BackgroundData on the clinical significance of iron deficiency (ID) in patients with myocardial infarction (MI) are conflicting. This may be related to the use of various ID criteria.We aimed to compare the association of different ID criteria with all-cause mortality after MI.MethodsConsecutive patients hospitalized for their first MI at a large tertiary heart center were included. We evaluated the association of different iron metabolism parameters measured on the first day after hospital admission with all-cause mortality.ResultsFrom the 1,156 patients included (aged 64±12 years, 25 % women), 194 (16.8 %) patients died during the median follow-up of 3.4 years. After multivariate adjustment, iron level ≤13 µmol/L (HR 1.67, 95 % CI 1.19–2.34) and the combination of iron level ≤12.8 µmol/L and soluble transferrin receptor (sTfR) ≥3 mg/L (HR 2.56, 95 % CI 1.64–3.99) termed as PragueID criteria were associated with increased mortality risk and had additional predictive value to the GRACE score. Compared to the model including iron level, the addition of sTfR improved risk stratification (net reclassification improvement 0.61, 95 % CI 0.52–0.69) by reclassifying patients into a higher-risk group. No association between ferritin level and mortality was found. 51 % of patients had low iron levels, and 58 % fulfilled the PragueID criteria.ConclusionIron deficiency is common among patients with the first MI. The PragueID criteria based on iron and soluble transferrin receptor levels provide the best prediction of mortality and should be evaluated in future interventional studies for the identification of patients potentially benefiting from intravenous iron therapy.

Objective: To evaluate the effect of smart device-based telerehabilitation on VO2peak in patients after myocardial infarction. Patients and Methods: This was a pilot, single-center, randomized, cross-over study with a 3-month intervention. One month after myocardial infarction, patients had cardiopulmonary exercise testing and a 6-minute walking test (6MWT) and were randomly assigned 1:1. In the intervention group, patients received a smartwatch to track the recommended number of steps, which was individualized and derived from the 6MWT. A study nurse telemonitored adherence to the recommended number of steps a day. In the control group, 150 minutes a week of moderate-intensity physical activity was recommended. After 3 months study arms were crossed over, and study procedures were repeated after 3 months. Results: Between June 1, 2019, and February 28, 2023, 64 patients were randomized, of which 61 (aged 51 +/- 10 years, 10% women) completed the study. Overall, the smart device-based telerehabilitation led to 2.31 mL/kg/min (95% CI, 1.25-3.37; P<.001) VO2peak increase compared with the control treatment. Furthermore, there was a significant effect on weight (-1.50 kg; 95% CI,-0.39 to-2.70), whereas the effect on the 6MWT distance (4.7 m; 95% CI,-11.8 to 21.1) or Kansas City Quality of Life questionnaire score (0.98; 95% CI,-1.38 to 3.35) was not significant. Conclusion: Smart device-based cardiac rehabilitation may be a promising alternative for patients unable or unwilling to attend in-person cardiac rehabilitation. Trial Registration: clinicaltrials.gov Identifier: NCT03926312 (c) 2024 THE AUTHORS. Published by Elsevier Inc on behalf of Mayo Foundation for Medical Education and Research. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) Mayo Clin Proc Digital Health 2024;2(3):352-360

Statins rank among the most useful drug groups with convincing data from clinical trials, especially in patients at very high risk of developing or recurring cardiovascular events of atherosclerotic origin. As with all effective drugs, side effects are described also for statins, but these effects are rare. Nevertheless, because statins are used by many individuals for a long time periods, these effects could be observed. The main discussed ones include myopathy, hepatopathy, decreased renal function and higher incidence of diabetes mellitus. Another area of recent discussions is the possibility of untoward effects of statins during extensive surgical procedures, when it is considered their discontinuation. However, the vast majority of available data demonstrated that statins are safe or even beneficial in terms of surgical procedures complications. Therefore, discontinuation of these drugs before surgery is not recommended in majority of individuals. Nevertheless, in certain risk groups statins could cause complications; these include patients with impaired renal function exposed to loading dose of statins before surgery. However, the presumption that the most serious complication of surgery might be unnecessary discontinuation of statins is still valid.

Abstract Background The associations of risk factors with vascular impairment in type 1 diabetes patients seem more complex than that in type 2 diabetes patients. Therefore, we analyzed the associations between traditional and novel cardiovascular risk factors and vascular parameters in individuals with T1D and modifications of these associations according to sex and genetic factors. Methods In a cross-sectional study, we analyzed the association of risk factors in T1D individuals younger than 65 years using vascular parameters, such as ankle brachial index (ABI) and toe brachial index (TBI), duplex ultrasound, measuring the presence of plaques in carotid and femoral arteries (Belcaro score) and intima media thickness of carotid arteries (CIMT). We also used photoplethysmography, which measured the interbranch index expressed as the Oliva-Roztocil index (ORI), and analyzed renal parameters, such as urine albumin/creatinine ratio (uACR) and glomerular filtration rate (GFR). We evaluated these associations using multivariate regression analysis, including interactions with sex and the gene for connexin 37 (Cx37) polymorphism (rs1764391). Results In 235 men and 227 women (mean age 43.6 ± 13.6 years; mean duration of diabetes 22.1 ± 11.3 years), pulse pressure was strongly associated with unfavorable values of most of the vascular parameters under study (ABI, TBI, Belcaro scores, uACR and ORI), whereas plasma lipids, represented by remnant cholesterol (cholesterol – LDL-HDL cholesterol), the atherogenic index of plasma (log (triglycerides/HDL cholesterol) and Lp(a), were associated primarily with renal impairment (uACR, GFR and lipoprotein (a)). Plasma non-HDL cholesterol was not associated with any vascular parameter under study. In contrast to pulse pressure, the associations of lipid factors with kidney and vascular parameters were modified by sex and the Cx37 gene. Conclusion In addition to known information, easily obtainable risk factor, such as pulse pressure, should be considered in individuals with T1D irrespective of sex and genetic background. The associations of plasma lipids with kidney function are complex and associated with sex and genetic factors. The decision of whether pulse pressure, remnant lipoproteins, Lp(a) and other determinants of vascular damage should become treatment targets in T1D should be based on the results of future clinical trials. Graphical Abstract

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Supported by Ministry of Health, Czech Republic - conceptual development of research organization 64165, General University Hospital in Prague, Czech Republic Background and Aims Elevated levels of plasma triglycerides (TG) have been identified as a risk factor for the development of cardiovacular disease, including acute coronary syndrome (ACS). Final TG levels are largely influenced by genetic factors. The most important genetic factors influencing TG levels in the Czech population are the polymorphisms in APOA5, GCKR, MAP3K1, CTF1, CYP26A1, LRP1, CILP2, LIPC, APOE, GALNT2 and LPL genes. Methods The variants in mentioned genes were analyzed in total 929 patients with ACS and 936 healthy controls (study post-MONICA). Only adult men under the age of 65 were included in the study. Results Plasma TG levels did not differ significantly between patients and controls (1.96 ± 1.30 mmol/L vs. 2.06 ± 1.47 mmol/L). CYP26A1 AA homozygotes (rs2068888) were more common (P <0.05; OR; 95% CI = 1.34; 1.03-1.74) among patients. The differences in the frequencies of the other variants were not statistically significant, however, with the exception of GCKR, LRP1, MAP3K1, GALNT2 and LPL variants, they were used to calculate the risk genetic score due to the higher OR value (above 1.15). Subjects with a score of 8 or more vs less than 3 occurred more frequently among patients with ACS than among controls (60% vs. 30%, P = 0.005; OR; 95% CI – 2.03; 1.24 – 3.31). Conclusions Genetic score calculated from six selected variants associated with plasma TG levels is a significant predictor of ACS in Czech Caucasian males.

Introduction: After myocardial infarction (MI), increasing functional capacity is an important goal of cardiac rehabilitation, that improves prognosis. However, standard cardiac rehabilitation is not accessible to many patients. Telemedicine programs are emerging as promising alternatives to in-person programs, but evidence confirming its benefits is lacking. Hypothesis: Smart device based remote cardiac rehabilitation can improve functional capacity assessed by VO2peak after MI. Methods: Patients were offered participation at the time of hospitalization for MI. One month after MI, patients underwent a cardiopulmonary exercise test, 6-minute walking test (6MWT) and were randomized 1:1. In the intervention group, patients received a smart watch to track the recommended number of steps, that was derived from the 6MWT. Adherence to the recommendations was telemonitored by a study nurse, with an over the phone motivation talk if compliance was unsatisfactory. In the control group, patients were recommended 150 minutes/week of moderate intensity exercise. Exercise stress tests were repeated after 3 months. Results: In total, 59 patients (mean age 51.5±10.4 years, 10.2% women, 67.8% STEMI, 96.6% PCI, mean discharge EF 48±10%) were included in the study. At baseline, there was no difference in clinical characteristics and functional capacity between the intervention (n=29) and control (n=30) groups. After 3 months of the intervention, VO2peak improved in the intervention arm with between group difference of 1.56 ml/kg/min (95%CI 0.06-3.05, p=0.041), with no difference in 6-minute walking distance (p=0.11). The effect of intervention differed by baseline functional capacity (p for interaction <0.01). Among patients with VO2peak at baseline ≤95% predicted, the between-group VO2peak difference after 3 months was 2.46 ml/kg/min (95% CI 0.78-4.13, p=0.005), and also oxygen uptake efficiency slope (between group difference 235, 95% CI 43-428, p=0.02) and 6-minute walking distance improved (between group difference 60m, 95% CI 1.5-119, p=0.045). Conclusions: Smart device based remote cardiac rehabilitation improves functional capacity after myocardial infarction, particularly in those with decreased functional capacity. NCT03926312

Cardiovascular diseases are characterized by many clinical, morphological, functional, and biochemical markers, including age, sex, genetic factors, plasma lipids, glycemia, and many other laboratory parameters [...]

Background The hypocretin/orexin system has been shown to play a role in heart failure. Whether it also influences myocardial infarction (MI) outcomes is unknown. We evaluated the effect of the rs7767652 minor allele T associated with decreased transcription of the hypocretin/orexin receptor-2 and circulating orexin A concentrations on mortality risk after MI. Methods and Results Data from a single-center, prospectively designed registry of consecutive patients hospitalized for MI at a large tertiary cardiology center were analyzed. Patients without previous history of MI or heart failure were included. A random population sample was used to compare allele frequencies in the general population. Out of 1009 patients (aged 64±12 years, 74.6% men) after MI, 6.1% were homozygotes (TT) and 39.4% heterozygotes (CT) for minor allele. Allele frequencies in the MI group did not differ from 1953 subjects from general population (χ2 P=0.62). At index hospitalization, MI size was the same, but ventricular fibrillation and the need for cardiopulmonary resuscitation were more prevalent in the TT allele variant. Among patients with ejection fraction ≤40% at discharge, the TT variant was associated with a lower increase in left ventricular ejection fraction during follow-up (P=0.03). During the 27-month follow-up, there was a statistically significant association of the TT variant with increased mortality risk (hazard ratio [HR], 2.83; P=0.001). Higher circulating orexin A was associated with a lower mortality risk (HR, 0.41; P<0.05). Conclusions Attenuation of hypocretin/orexin signaling is associated with increased mortality risk after MI. This effect may be partially explained by the increased arrhythmic risk and the effect on the left ventricular systolic function recovery.