Right ventricle to pulmonary artery coupling as a predictor of perioperative outcome in patients with secondary mitral valve insufficiency.

BACKGROUND: The aim of the study was to assess some parameters of right ventricle (RV) function as predictors of short-term mortality in patients with severe secondary mitral regurgitation (SMR) after mitral valve surgery. METHODS: We conducted a retrospective analysis of 112 consecutive patients with severe SMR who had undergone mitral valve repair or replacement with or without concomitant coronary artery bypass surgery. We assessed RV to pulmonary artery coupling by calculating the ratio of tricuspid annular plane systolic excursion (TAPSE) to non-invasively estimated RV systolic pressure (RVSP). The study endpoint was 30 days post-procedural mortality. RESULTS: Overall, the 30-day mortality was 6%. TAPSE/RVSP ratio < 0.42 mm/mmHg was a significant predictor of mortality and remained so after adjusting for age and sex. The Kaplan-Meier survival analysis showed that patients with RVSP > 55 mmHg and those with TAPSE/RVSP ratio < 0.42 mm/mmHg had a lower survival probability. CONCLUSIONS: TAPSE/RVSP < 0.42 mm/mmHg is a strong predictor of short-term mortality in patients with SMR when considered for valve surgery.

Predictive value of metabolic score for insulin resistance and triglyceride glucose-BMI among patients with acute myocardial infarction in 1-year follow-up.

BACKGROUND: Recently two indicators - metabolic score for insulin resistance (METS-IR) and triglyceride glucose-BMI (TyG-BMI) have been proposed as surrogate markers of IR and potential cardiovascular risk factors. The aim of the study was to assess the predictive value of METS-IR and TyG-BMI concerning the incidence of major adverse cardiovascular events (MACE) and all-cause mortality in 1-year follow-up among patients admitted with acute myocardial infarction (AMI). METHODS: Two thousand one hundred fifty-three patients with a median age of 68 years were enrolled in the study. Patients were divided into two groups according to the type of AMI. RESULTS: MACE occurred in 7.9% of the patients in the ST-segment elevation myocardial infarction (STEMI) group and in 10.9% of the non-STEMI (NSTEMI) group. No significant difference in median MACE-IR and TyG-BMI between patients with and without incidence of MACE was found in both groups. None of the examined indices were predictors of MACE in the STEMI and NSTEMI groups. Moreover, both of them did not predict MACE in subgroups of patients classified according to the presence of diabetes. Finally, METS-IR and TyG-BMI were significant predictors of 1-year morality, however with low prognostic value and only in univariate regression analysis. CONCLUSION: METS-IR and TyG-BMI should not be used in predicting MACE among patients with AMI.

Comparison of the population of Polish patients participating in the TRANSITION study with the international population: a post hoc analysis.

INTRODUCTION: Heart failure (HF) patients discharged from a hospital are at a high risk of death and rehospitalization. Scarce data are available on the use of sacubitril / valsartan in this population in Poland. OBJECTIVE: The aim of this study was to compare the efficacy and tolerability of sacubitril / valsartan in the group of Polish patients who participated in the TRANSITION study with the patients recruited at other sites. PATIENTS AND METHODS: This is a post hoc secondary analysis of the TRANSITION study comparing sacubitril / valsartan initiation pre- vs postdischarge in 991 patients hospitalized for acute decompensated HF with reduced ejection fraction (HFrEF). The Polish subgroup consisted of 104 patients. RESULTS: Significant differences were identified in the characteristics of Polish vs non­Polish populations. At baseline, the Polish population showed higher proportion of men, higher body mass index, lower heart rate, N­terminal pro-B­type natriuretic peptide and high­sensitivity troponin T levels, and significantly lower New York Heart Association class. The Polish patients were better managed in terms of implanted electrotherapy devices, percutaneous coronary interventions, and drug therapy, and were more often hospitalized. The primary end point of achieving the target dose of sacubitril / valsartan at treatment week 10 was met by 45.6% of the Polish patients and 48.4% of the non­Polish population (P = 0.61). Approximately 90% of the Polish patients received and maintained any sacubitril / valsartan dose for 2 weeks over 10­week treatment vs 87.5% of the non­Polish patients (P = 0.36). The rate of permanent sacubitril / valsartan treatment discontinuation was low in both Polish (3.9%) and non­Polish populations (6.4%) (P = 0.33). CONCLUSIONS: Sacubitril / valsartan can be used safely in the early period after an episode of acute HF both in the Polish and non­Polish patients with HFrEF, and the likelihood to achieve the maximum dose is the same despite significant differences between the studied populations.

Prognostic significance of atherogenic index of plasma, atherogenic coefficient and lipoprotein combined index among elderly patients with non-ST-segment elevation myocardial infarction in 1-year follow-up.

OBJECTIVES: Coronary artery disease (CAD) remains a leading cause of death in elderly patients. Recently, novel lipoproteins- Atherogenic Index of Plasma (AIP), Atherogenic Coefficient (AC) and Lipoprotein Combine Index (LCI) have been suggested as CAD risk factors; their clinical usefulness, however, remains unknown. The aim of the study was to assess the predictive value of AIP, AC and LCI concerning incidence of major adverse cardiovascular events (MACE) and all-cause mortality in 1-year follow-up. METHODS: For the study, 1,083 patients, aged 60 or older, with NSTEMI were enrolled and divided into two groups: young-old and old-old. RESULTS: MACE occurred in 11.8 % of the patients; LCI showed a borderline significance, but only in univariate analysis. Analysis in groups revealed ambiguous results. None of the examined indices was a predictor of MACE in the young-old group whereas all three of them were significant, but negative predictors in the old-old group. Finally, all-cause mortality at follow-up was 14.9 %. AC predicted 1-year mortality in the whole study population (OR = 1.1 (95% CI: 1-1.2; p = 0.02), but was insignificant in the multivariable model. Additionally, it was an independent predictor in the old-old group, but with borderline significance (OR = 1.14 (95% CI: 1-1.3, p = 0.036). CONCLUSIONS: AIP, AC and LCI should not be used as predictors of MACE and 1-year mortality among elderly patients with NSTEMI (Tab. 5, Ref. 23).

Prognostic value of non-traditional lipid parameters: Castelli Risk Index I, Castelli Risk Index II, and triglycerides to high-density lipoprotein cholesterol ratio among patients with non-ST-segment elevation myocardial infarction during 1­year follow-up.

Aim    Concentrations of classical lipoproteines have a well-established role in non-invasive cardiology. The efficacy of the Castelli Risk Index I (CRI I), Castelli Risk Index II (CRI II), and triglycerides to high-density lipoprotein cholesterol (TG / HDL-C) ratio in clinical practice are currently under evaluation. The study aimed to assess the predictive value of CRI I, CRI II and TG / HDL-C for the incidence of Major Adverse Cardiovascular Events (MACE) and for all-cause mortality during 1­year follow-up of patients with non-ST-segment elevation myocardial infarction (NSTEMI).Material and Methods    1,301 patients were enrolled in the study. Associations between CRI I, CRI II, TG / HDL-C and occurrence of MACE and 1­year mortality were studied. Moreover correlations between CRI I, CRI II, and TG / HDL-C and the severity of coronary artery disease (CAD) were assessed.Results    MACE occurred in 10.9 % (142) of patients, and 1­year mortality was 13.4 % (174). None of the evaluated indices appeared to be an independent predictor of MACE in either the entire population or subpopulations, as divided according to the presence of diabetes or CAD diagnosed prior to admission. Furthermore, no dependence between 1­year mortality and the examined indices was found. Additionally, only a weak correlation between CAD severity and CRI I was observed (R=0.08, p=0.02). No significant correlations for CRI II (p=0.07) and TG / HDL-C (p=0.6) were detected.Conclusions    CRI I, CRI II and TG / HDL-C should not be used as predictors of MACE or all-cause mortality among patients with NSTEMI. Moreover, these indices do not reflect CAD severity.

Links between chronic exposure to outdoor air pollution and cardiovascular diseases: a review.

Acute exposure to air pollution is associated with an increasing risk of death and cardiovascular disorders. Nonetheless, the impact of chronic exposure to air pollution on the circulatory system is still debated. Here, we review the links of chronic exposure to outdoor air pollution with mortality and most common cardiovascular diseases, in particular during the coronavirus disease 2019 event (COVID-19). We found that recent studies provide robust evidence for a causal effect of chronic exposure to air pollution and cardiovascular mortality. In terms of mortality, the strongest relationship was noted for fine particulate matter, nitrogen dioxide, and ozone. There is also increasing evidence showing that exposure to air pollution, mainly fine particulate matter and nitrogen dioxide, is associated with the development of atherosclerosis, hypertension, stroke, and heart failure. However, available scientific evidence is not strong enough to support associations with cardiac arrhythmias and coagulation disturbances. Noteworthy, for some pollutants, the risk of negative health effects is high for concentrations lower than the limit values recommended by the European Union and Word Health Organization. Efforts to diminish exposure to air pollution and to design optimal methods of air pollution reduction should be urgently intensified and supported by effective legislation and interdisciplinary cooperation.

Prognostic value of the triglyceride-glucose index among non-diabetic patients with acute myocardial infarction at one-year follow-up.

BACKGROUND: The triglyceride-glucose index (TyG index) is a novel metabolic marker initially used as an indicator of insulin resistance. Recently, its use as a cardiovascular risk factor has been taken into consideration; however, there is a shortage of evidence for its clinical importance. AIMS: The study aimed to assess the relationship between the TyG index = ln (fasting triglyceride [mg/dl] × fasting glucose [mg/dl]/2) and the incidence of major adverse cardiovascular events (MACE) at a 1-year follow-up among non-diabetic patients with acute myocardial infarction (MI). In addition, the predictive value of the TyG index concerning all-cause mortality in the study group was evaluated. METHODS: For the study, 1340 non-diabetic patients with acute MI (median age, 67 years, 70.4% male) were consecutively enrolled between 2013 and 2019. The fasting lipid profile and the fasting glucose level were assessed within 24 hours of admission. RESULTS: MACE occurred in 8.13 % (n = 109) of the study group, whereas 1-year mortality rate was 14.5% (n = 195). There was no difference in the median TyG index value among patients with and without incidence of MACE at a 1-year follow-up (8.73 [8.36-9.08] vs. 8.81 [8.5-9.17]; P = 0.09). Moreover, the TyG index was not a predictor of these events (P = 0.06). In multivariable regression analysis, only previously diagnosed coronary artery disease (CAD) was an independent predictor of MACE (odds ratio [OR], 1.54; 95% CI, 1.02-2.32; P = 0.03). Finally, the TyG index was not an indicator of all-cause mortality (P = 0.25). CONCLUSIONS: The TyG index should not be used as a predictor of MACE and all-cause mortality among non-diabetic patients with MI at a 1-year follow-up.

Right ventricular echocardiographic parameters associated with prothrombotic abnormalities in normotensive patients with acute pulmonary embolism.

BACKGROUND: In acute pulmonary embolism (PE) right ventricular (RV) pressure overload negatively affects prognosis. Recently we have shown that RV dilatation is associated with a prothrombotic state in PE. We investigated which RV echocardiographic parameters best indicate prothrombotic alterations in acute PE. METHODS: In 121 normotensive, noncancer PE patients, markers of RV dilatation and dysfunction were evaluated on admission using transthoracic echocardiography, along with prothrombotic state markers, i.e. increased endogenous thrombin generation (ETP), low fibrin clot permeability (Ks, a measure of clot density), and prolonged clot lysis time (CLT). RESULTS: RV parasternal long axis (RVOT PLAX) >30 mm was associated with ETP (OR 3.86; 95% CI 1.55-9.62; p = 0.004) and CLT (OR 4.08; 95% CI 1.58-10.54; p = 0.004) in the top quartiles, but not with Ks. RV short parasternal axis (RVOT PSAX) >27 mm showed similar associations with higher ETP (OR 3.54; 95% CI 1.50-8.37; p = 0.004) and prolonged CLT (OR 2.78; 95% CI 1.17-6.62; p = 0.021). RV basal diameter >41 mm solely predicted prolonged CLT (OR 2.93; 95% CI 1.23-6.99; p = 0.016). The right atrium area, pulmonary trunk diameter, and tricuspid regurgitation maximum velocity were not related to prothrombotic markers, except for tricuspid annular plane systolic excursion weakly associated with ETP. Multivariable analysis showed that RVOT PSAX is independently associated with prolonged CLT (OR 1.16; 95% CI 1.04-1.30; p = 0.007), low Ks (OR 1.21; 95% CI 1.02-1.44; p = 0.029), and higher ETP (OR 1.14; 95% CI 1.03-1.26; p = 0.009). CONCLUSIONS: Among RV echocardiographic parameters, the RVOT dilatation measured in PSAX best predicts prothrombotic alterations in PE patients.

Subclinical cardiac performance in obese and overweight women as a potential risk factor of preeclampsia.

OBJECTIVES: Failure to increase cardiac output owing to suboptimal cardiac performance in obese women may contribute to placental hypoperfusion, and therefore subsequently to the abnormal placental development. The aim of this study was to evaluate the relationship between left ventricle (LV) function in overweight and obese pregnant women and parameters of blood flow in uterine arteries. STUDY DESIGN AND MAIN OUTCOME MEASURES: We conducted a prospective cohort study, which included consecutive 87 women with singleton pregnancy - 56 women with normal weight and 31 overweight and obese women. During pregnancy blood pressure, echocardiography and the assessment of blood flow in uterine arteries - pulsatility index (PI) and resistance index (RI) were assessed on two visits (V): V1 between 10 and 14 weeks and V2 between 25 and 30 weeks of gestation. A stepwise logistic regression analysis was performed to determine the independent predictors of upper quartile of RI and PI during V2 in the study population. RESULTS: The multivariate logistic regression analysis showed that LVCI and LV mass measured on V1 were the only independent predictors of upper quartile of RI during V2, whereas LVCI was the only independent predictor of upper quartile of PI during V2. CONCLUSIONS: Subclinical left ventricle dysfunction in obese and overweight women, present from the first trimester, may contribute to placental hypoperfusion and higher resistance in uterine arteries later during pregnancy. This may lead in some women to preeclampsia.

Electrocardiographic identification of the culprit coronary artery in acute non-ST-elevation myocardial infarction: predictive value of N-wave and T-wave precordial instability.

BACKGROUND: Recently, novel ischemic electrocardiographic changes have been described, which may be clinically significant in the identification of the culprit coronary vessel in patients with non-ST-elevation myocardial infarction (NSTEMI). We sought to determine the predictive value of N-wave, T-wave precordial instability, de-Winter ST/T-wave complex, and inferolateral myocardial infarction in the identification of the culprit artery in patients with NSTEMI referred for early invasive (<24 h) treatment. METHODS: A total of 148 patients with NSTEMI, aged 40-91 years, were enrolled from a cohort of 510 consecutive NSTEMI subjects, hospitalized in our center in 2015-2017. RESULTS: Of the evaluated ischemic ECG changes, the most common finding in patients with culprit left circumflex (LCx)/obtuse marginal artery or right coronary artery was T-wave precordial instability (28.3 and 13.5%, respectively), whereas in individuals with culprit left anterior descending/diagonal artery, T-wave precordial instability and N-wave in leads II, III or aVF occurred equally often (16.0%). A significant relationship was found between the occurrence of N-wave in inferolateral leads and culprit LCx/obtuse marginal. In multivariable analysis, N-wave in lead aVL [odds ratio (OR) 2.10; 95% confidence interval (CI), 1.15-3.81], and T-wave precordial instability (OR 1.56; 95% CI, 1.02-2.41) were independent predictors of culprit LCx/obtuse marginal. The accuracy of N-wave in lead aVL in predicting the culprit LCx/obtuse marginal was 73.9% and was higher than the accuracy of T-wave precordial instability, which was 69.1%. CONCLUSIONS: In patients with NSTEMI referred for early invasive treatment, the presence of N-wave or T-wave precordial instability may be of greater clinical importance in the prediction of culprit LCx/obtuse marginal than classic ischemic changes.

Relationship among the leptin-to-adiponectin ratio, systemic inflammation, and anisocytosis in well-controlled type 2 diabetic patients with atherosclerotic cardiovascular disease.

BACKGROUND: Previous studies have shown that red blood cell distribution width (RDW) is an independent predictor of poor prognosis in type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). The mechanisms underlying increased anisocytosis in patients with T2D and confirmed ASCVD remain poorly understood. AIMS: We sought to evaluate the relationship among the leptin-to-adiponectin ratio, systemic low -grade inflammation, and RDW in optimally treated patients with T2D and established ASCVD. METHODS: A total of 68 patients, aged 47 to 85 years (mean [SD], 65.3 [6.8] years) and including 21 women (30.9%), were enrolled and grouped according to median RDW into those with RDW <13.5% (n = 33) and those with RDW ≥13.5% (n = 35). RESULTS: Patients with RDW ≥13.5% had a significantly higher median (interquartile range [IQR]) serum leptin-to-adiponectin ratio (1.7 [0.49-2.3] ng/µg vs 0.66 [0.31-1.25] ng/µg; P = 0.04) and median (IQR) tumor necrosis factor α levels (1.58 [1.42-1.97] pg/ml vs 1.39 [1.18-1.57] pg/ml; P = 0.02). There were no significant differences in the concentrations of other inflammatory markers. The leptin-to-adiponectin ratio (r = 0.25; P = 0.04) and levels of tumor necrosis factor α (r = 0.32; P = 0.01) and soluble intercellular adhesion molecule 1 (r = 0.31; P = 0.01) were positively correlated with RDW, which was confirmed by univariate linear regression analysis. A multivariable regression model, which included demographic, clinical, and laboratory data, showed that white blood cell count (ß = 0.25; 95% CI, 0.05-0.45; P = 0.01), soluble intercellular adhesion molecule 1 levels (ß = 0.21; 95% CI, 0.02-0.41; P = 0.03), and mean corpuscular hemoglobin concentration (MCHC), (ß = -0.48; 95% CI, 0.67 to -0.28; P < 0.001) were independent predictors of RDW in our patients. CONCLUSIONS: In well-controlled patients with T2D and ASCVD, the RDW values are associated with leptin-to-adiponectin imbalance and selected inflammatory markers.

Unsaturated fatty acid composition in serum phospholipids in patients in the acute phase of myocardial infarction.

BACKGROUND: Recent improvements in optimal cardiovascular therapy have questioned the beneficial effects of polyunsaturated fatty acids (PUFAs) observed in previous studies. AIMS: We investigated the fatty acid (FA) composition in serum phospholipids in patients with an established acute phase of myocardial infarction (MI) and in high­risk patients with stable atherosclerotic cardiovascular disease (CVD). METHODS: We studied 83 patients hospitalized within 12 hours from the onset of the first clinical symptoms of MI. As a control group, we assessed 74 patients at high cardiovascular risk with an established stable atherosclerotic CVD treated at an outpatient cardiology clinic. Gas chromatography was used to evaluate the FA composition in serum phospholipids in both groups. RESULTS: The final analysis included 52 patients with acute MI and 74 controls. In both groups, saturated FAs constituted the largest fraction of serum phospholipid FAs (median, 1574.67 µmol/l), followed by n­6 PUFAs (median, 1106.99 µmol/l). The levels of total saturated FAs, monounsaturated FAs, n­6 PUFAs, as well as the ratio of n­6 to n­3 PUFAs significantly differed between groups. Palmitic acid constituted the largest fraction of serum phospholipids both in patients and controls (31.9% and 31.16%, respectively). In a multivariate logistic regression analysis, body mass index, low­density lipoprotein cholesterol, aspartate aminotransferase, high­sensitivity C­reactive protein, and palmitoleic and eicosadienoic acids were independently associated with MI. CONCLUSIONS: We showed major differences in the FA composition of serum phospholipids between patients with acute MI and high­risk individuals with stable atherosclerotic CVD. Eicosadienoic and palmitoleic acids, apart from typical cardiovascular risk factors, were independently associated with MI.

Predictive value of electrocardiographic ST­segment elevation myocardial infarction equivalents for detecting acute coronary artery occlusion in patients with non-ST­segment elevation myocardial infarction.

BACKGROUND: The sensitivity and accuracy of 12-lead ECG for the detection of acute total occlusion (TO) of the culprit coronary artery in non-ST-elevation myocardial infarction (NSTEMI) is still suboptimal, particularly for posterolateral circulation.   Aims: We evaluated the prevalence and predictive value of electrocardiographic STEMI-equivalents (i.e. de-Winter ST/T-wave complex, N-wave, T-wave precordial instability, and posterior myocardial infarction) for detecting acute coronary artery occlusion in NSTEMI patients referred for early invasive treatment. METHODS: A total of 165 NSTEMI patients were enrolled. The patients were grouped according to the coronary angiography findings into those with TO (TIMI 0) in the culprit artery (n=43) and those with preserved flow in this vessel (TIMI 1-3) (n=122). RESULTS: The main findings of this study were as follows: 1) 31.5% of patients had at least one STEMI-equivalent, mostly N-wave in lead II, III or aVF; 2) the most common STEMI-equivalent in subjects with acute TO was T-wave precordial instability; 3) there was a significant relationship between the prevalence of STEMI-equivalents and acute coronary artery occlusion; 4) among all evaluated ECG parameters, only ST-segment depression in leads I, aVL, V6 was an independent predictor of acute TO in multivariate analysis; 5) ST-segment depression in leads I, aVL, V6 had higher specificity, positive and negative predictive values as well as accuracy in predicting acute TO of the culprit vessel, as compared to STEMI-equivalents. CONCLUSIONS: STEMI-equivalents do not seem to have a relevant advantage over classic ischaemic ECG changes in the prediction of acute coronary artery occlusion in NSTEMI patients.

Association between carotid-femoral pulse wave velocity and overall cardiovascular risk score assessed by the SCORE system in urban Polish population.

BACKGROUND: The Systemic COronary Risk Estimation (SCORE) system is recommended for the assessment of cardiovascular disease (CVD) death risk in individuals free of CVD. AIM: We sought to determine the association between carotid-femoral pulse wave velocity (CFPWV) and SCORE. METHODS: The study involved 1008 Krakow residents, and a random subsample of 3424 men and 3205 women who participated in Wave 2 of the Polish part of the Health, Alcohol, and Psychosocial factors in Eastern Europe (HAPIEE) study. At baseline we performed a medical interview, physical examination, evaluation of present comorbidities, medications using standardised methods. A follow-up of 4.9 years included measurement of CFPWV using an automatic, computerised Complior® system. RESULTS: Final analysis included 720 patients (378 women), aged 58.5 ± 6.5 years at baseline. In 488 individuals without his- tory of CVD and/or diabetes, SCORE was calculated. Median CFPWV was higher (p = 0.002) in men (12.5 m/s; interquartile range [IQR] 10.3-15.7) than in women (11.7 m/s; IQR 10.1-13.7). High CFPWV (> 10 m/s) was observed in 270 men (78.9%) and in 285 women (75.4%). We observed a strong association between high CVD risk (SCORE ≥ 5%) and high CFPWV (odds ratio 2.29; 95% confidence interval 1.17-4.46). The CFPWV cut-off value to differentiate between patients with low and high CVD risk was 11.7 m/s (with 58.6% sensitivity and 71.3% specificity, AUC = 0.68). CONCLUSIONS: Our study is the first to describe the distribution of CFPWV in the adult Polish population. SCORE ≥ 5% pre- dicted high CFPWV in 4.9 years of follow-up, which was independent of other risk factors. CFPWV > 11.7 m/s was most valid in relation to high CVD risk.

Plasma Protein Oxidation as a Determinant of Impaired Fibrinolysis in Type 2 Diabetes.

OBJECTIVE: We investigated clinical and laboratory determinants of plasma protein oxidation and its associations with clot fibrinolysis in type 2 diabetes patients. MATERIALS AND METHODS: Our cross-sectional study consisted of 246 type 2 diabetic patients, 143 (58%) with concomitant cardiovascular disease (CVD), including 41 (17%) with previous myocardial infarction (MI). We measured total protein carbonylation (PC), thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) along with clot lysis time (CLT) and clot permeation (Ks ), fibrinogen, plasminogen, α-2-antiplasmin, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI) and thrombomodulin. RESULTS: Total PC correlated positively, while TAC correlated inversely with glycated haemoglobin and diabetes duration (all p < 0.05). Diabetic patients with CVD had higher total PC, TBARS and lower TAC compared with the remainder (all p < 0.001). Among correlations of total PC with Ks , PAI-1, thrombomodulin and TAFI, the strongest was with CLT (r = 0.687, all p < 0.01). High total PC, defined as ≥ 3.45 nmol/mg, was predicted by time since diabetes diagnosis ≥ 5 years (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.36-6.63) and previous MI (OR: 11.31, 95% CI: 4.37-29.32). After adjustment for potential confounders, total PC accounted for 34.9% of the total variance in CLT. Total PC at a cut-off of 3.44 nmol/mg showed high discriminatory power for identifying patients with prolonged CLT (area under the curve: 0.845, 95% CI: 0.792-0.898, p < 0.001). CONCLUSION: Elevated plasma PC, largely driven by a long history of diabetes and concomitant CVD, is an important determinant of hypofibrinolysis in type 2 diabetes.

Polyhedrocytes in blood clots of type 2 diabetic patients with high cardiovascular risk: association with glycemia, oxidative stress and platelet activation.

BACKGROUND: Little is known about factors that affect the composition of contracted blood clots in specific diseases. We investigated the content of polyhedral erythrocytes (polyhedrocytes) formed in blood clots and its determinants in type 2 diabetes (T2D) patients. METHODS: In 97 patients with long-standing T2D [median HbA1c, 6.4% (interquartile range 5.9-7.8)], we measured in vitro the composition of blood clots, including a clot area covered by polyhedrocytes using scanning electron microscopy and the erythrocyte compression index (ECI), defined as a ratio of the mean polyhedrocyte area to the mean native erythrocyte area. Moreover, plasma fibrin clot permeability (Ks), clot lysis time (CLT), thrombin generation, oxidative stress [total protein carbonyl (total PC), total antioxidant capacity and thiobarbituric acid reactive substances (TBARS)], and platelet activation markers were determined. The impact of glucose concentration on polyhedrocytes formation was assessed in vitro. RESULTS: Polyhedrocytes content in contracted clots was positively correlated with glucose (r = 0.24, p = 0.028), glycated hemoglobin (r = 0.40, p = 0.024), total cholesterol (r = 0.22, p = 0.044), TBARS (r = 0.60, p = 0.0027), P-selectin (r = 0.54, p = 0.0078) and platelet factor-4, PF4 (r = 0.59, p = 0.0032), but not with thrombin generation, platelet count, Ks or CLT. Patients who formed more polyhedrocytes (≥ 10th percentile) (n = 83, 85.6%) had higher glucose (+ 15.7%, p = 0.018), fibrinogen (+ 16.6%, p = 0.004), lower red blood cell distribution width (RDW, - 8.8%, p = 0.034), reduced plasma clot density (- 21.8% Ks, p = 0.011) and impaired fibrinolysis (+ 6.5% CLT, p = 0.037) when compared to patients with lesser amount of polyhedrocytes (< 10th percentile). ECI and the content of polyhedrocytes were strongly associated with total PC (r = 0.79, p = 0.036 and r = 0.67, p = 0.0004, respectively). In vitro an increase of glucose concentration by 10 mmol/L was associated with 94% higher polyhedrocytes content (p = 0.033) when compared to the baseline (7.1 mM). After adjustment for age, sex and fibrinogen, multiple regression analysis showed that RDW was the only independent predictor of polyhedrocytes content in T2D (OR = 0.61, 95% CI 0.39-0.92). CONCLUSIONS: Poor glycemic control, together with enhanced platelet activation and oxidative stress, increase the content of polyhedrocytes in blood clots generated in T2D patients.