Proteoglycan Remodeling Is Accelerated in Females with Angina Pectoris and Diffuse Myocardial Fibrosis: the iPOWER Study.

Angina and no obstructive coronary artery disease (CAD) have an unfavorable prognosis, possibly due to diffuse myocardial fibrosis (DMF). In DMF the proteoglycans biglycan and versican are actively remodeled by matrix metalloproteinase. We investigated biglycan and versican in females with angina and possible DMF assessed by cardiac magnetic resonance (CMR). Seventy-one females with angina and no obstructive CAD were included. Asymptomatic females served as controls. Versican and biglycan were measured and CMR was performed measuring extracellular volume. Biglycan and versican levels were higher in symptomatic females compared with controls; 31.4 ng/mL vs. 16.4 ng/mL (p < 0.001) and 2.1 ng/mL vs. 1.8 ng/mL (p < 0.001) and moderately correlated to extracellular volume (r2 = 0.38, p<0.001 and r2 = 0.26, p = 0.015). Turnover of biglycan and versican was increased in angina females compared with controls and associated with extracellular volume, supporting a link between angina with no obstructive CAD and fibrotic remodeling.

Inflammation, non-endothelial dependent coronary microvascular function and diastolic function-Are they linked?

PURPOSE: Systemic inflammation and coronary microvascular dysfunction (CMD) may be causal drivers of heart failure with preserved ejection fraction (HFpEF). We tested the hypothesis that subclinical inflammation is associated with non-endothelial dependent CMD and diastolic dysfunction. METHODS: In a cross-sectional study of 336 women with angina but no flow limiting coronary artery stenosis (180 with diabetes) and 95 asymptomatic controls, blood samples were analysed for 90 biomarkers of which 34 were part of inflammatory pathways. CMD was assessed as coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography and defined as CFVR<2.5. We used E/e' as an indicator of diastolic function in age-adjusted linear regressions to assess correlations between biomarkers, CFVR and diastolic function. RESULTS: CMD was found in 59% of participants whereas only 4% fulfilled strict criteria for diastolic dysfunction. Thirty-five biomarkers, 17 of them inflammatory, were negatively correlated with CFVR and 25, 15 inflammatory, were positively correlated with E/e'. A total of 13 biomarkers, 9 inflammatory, were associated with both CFVR and E/e'. CFVR and E/e' were only correlated in the subgroup of patients with CMD and signs of increased filling pressure (E/e'>10) (p = 0.012). CONCLUSION: This is the first study to link a large number of mainly inflammatory biomarkers to both CMD and E/e', thus confirming a role of inflammation in both conditions. However, despite a high prevalence of CMD, few patients had diastolic dysfunction and the data do not support a major pathophysiologic role of non-endothelial dependent CMD in diastolic dysfunction.

Network pharmacology-based therapeutic mechanism of Kuanxiong aerosol for angina pectoris.

ETHNOPHARMACOLOGICAL RELEVANCE: Kuanxiong aerosol has been reported to be an effective and safe clinical treatment for angina pectoris (AP). AIM OF THE STUDY: To explore the potential pharmacological mechanism of Kuanxiong aerosol by combined methods of network pharmacology prediction and experimental verification. MATERIALS AND METHODS: Networks of Kuanxiong aerosol-associated targets and AP-related genes were constructed through STRING database. Potential targets and pathway enrichment analysis related to the therapeutic efficacy of Kuanxiong aerosol were identified using Cytoscape and Database for Annotation, Visualization and Integrated Discovery (DAVID). To explore the mechanism of action of Kuanxiong aerosol, its in vitro effects on myocardial hypoxia, inflammatory cytokines, and oxidative injury, and its in vivo pharmacological effects on myocardial ischemia and cardiac fibrosis were studied in rat models. RESULTS: Network pharmacology analysis revealed that the potential targets mainly include the Fas ligand (FASLG), interleukin 4 (IL4), and catalase (CAT), which mediated the processes of apoptosis, and cellular responses to hypoxia, lipopolysaccharide (LPS), reactive oxygen species (ROS), and mechanical stimulus. Multiple pathways, such as the hypoxia-inducible factor 1 (HIF1) and tumor necrosis factor (TNF) pathways were found to be closely related to the pharmacological protective mechanism of Kuanxiong aerosol against AP. In addition, Kuanxiong aerosol suppressed the hypoxia, LPS, and hydrogen peroxide (H2O2)-induced injuries of H9c2 cardiomyocytes through the regulation of HIF1A, suppressed expression of IL6 and TNF, and antioxidant property. In the rat model of myocardial ischemia, Kuanxiong aerosol was found to lower the creatine kinase (CK), creatine kinase-myocardial band (CK-MB), and lactate dehydrogenase (LDH) levels, without altering the hemodynamic function. Kuanxiong aerosol was capable of attenuating cardiac fibrosis and improving cardiac function in a cardiac fibrosis rat model. CONCLUSIONS: This study revealed that the pharmacological mechanisms of Kuanxiong aerosol for AP therapy were related to anti-myocardial ischemia, anti-inflammation, and anti-oxidation via a non-hemodynamic manner, indicating that Kuanxiong aerosol is a preferable drug clinically for AP treatment due to its both preventive and protective effects.

Gender differences in thrombogenicity among patients with angina and non-obstructive coronary artery disease.

Women more often present with angina and non-obstructive coronary artery disease (ANOCA) and have poorer clinical outcomes than men. These findings may be related to sex associated differences in inflammation and thrombogenicity. Consecutive patients (n = 134) with ANOCA (luminal diameter stenosis < 50%) undergoing elective cardiac catheterization were included in post hoc analysis of Multi-Analyte, thrombogenic, and Genetic Markers of Atherosclerosis (MAGMA, NCT01276678) study. Patients with prior revascularization, coronary artery bypass grafting or myocardial infarction were excluded. Blood for thromboelastography, oxidized LDL ß2-glycoprotein complex (AtherOx), oxidized-LDL, lipid profile, and urine for 11-dehydrothromboxane B2 (dTxB2) were obtained before catheterization. All women (n = 75) were post-menopausal and tended to be older than men (61.4 ± 10.6 vs. 58.6 ± 9.9 year, p = 0.12), and were significantly more thrombogenic with higher thrombin-induced platelet-fibrin strength (TIP-FCS, mm) (68.0 ± 4.5 vs. 64.5 ± 6.2 mm, p = 0.001), clotting index (0.35 ± 2.22 vs. - 0.72 ± 2.75, p = 0.02), K (measure of the speed to reach 20 mm of clot strength from an amplitude of 2 mm) (2.2 ± 1.6 vs. 1.7 ± 0.5 min, p = 0.01), and fibrinogen activity (degrees) (66.6 ± 7.1 vs. 62.9 ± 7.5, p = 0.009). Markers of inflammation were not significantly different between the two groups. Women had higher total cholesterol, total LDL, LDL subtypes 1 and 2, total HDL, HDL subtypes 2 and 3, and ApoA1 (p < 0.05 for all). On multivariate regression, TIP-FCS remained significantly higher in women (p < 0.0001). Women with ANOCA are more thrombogenic than men. This fundamental difference in thrombogenicity may affect gender-related outcomes and warrants further investigation.

Statins for the Primary Prevention of Coronary Heart Disease.

OBJECT: The purpose of this study was to fully assess the role of statins in the primary prevention of coronary heart disease (CHD). METHODS: We searched six databases (PubMed, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database, and Chinese Scientific Journal Database) to identify relevant randomized controlled trials (RCTs) from inception to 31 October 2017. Two review authors independently assessed the methodological quality and analysed the data using Rev Man 5.3 software. Risk ratios and 95% confidence intervals (95% CI) were pooled using fixed/random-effects models. Funnel plots and Begg's test were conducted to assess publication bias. The quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Sixteen RCTs with 69159 participants were included in this review. Statins can effectively decrease the occurrence of angina (RR=0.70, 95% CI: 0.58~0.85, I2 =0%), nonfatal myocardial infarction (MI) (RR=0.60, 95% CI: 0.51~0.69, I2 =14%), fatal MI (RR=0.49, 95% CI: 0.24~0.98, I2 =0%), any MI (RR=0.53, 95% CI: 0.42~0.67, I2 =0%), any coronary heart events (RR=0.73, 95% CI: 0.68~0.78, I2=0%), coronary revascularization (RR=0.66, 95% CI: 0.55~0.78, I2 = 0%), and any cardiovascular events (RR=0.77, 95% CI: 0.72~82, I2 = 0%). However, based on the current evidence, there were no significant differences in CHD deaths (RR=0.82, 95% CI: 0.66~1.02, I2=0%) and all-cause mortality (RR=0.88, 95% CI: 0.76 ~1.01, I2 =58%) between the two groups. Additionally, statins were more likely to result in diabetes (RR=1.21, 95% CI: 1.05~1.39, I2 =0%). There was no evidence of publication biases, and the quality of the evidence was considered moderate. CONCLUSION: Statins seemed to be beneficial for the primary prevention of CHDs but have no effect on CHD death and all-cause mortality.

Incomplete coronary sinus reducer endothelialization as potential mechanism of clinical failure.

The number of patients suffering from refractory angina is constantly increasing. Moreover, these patients are considered at higher risk for new hospitalizations and increased incidence of adverse cardiac events. The coronary sinus reducer was recently introduced as a new therapeutic option in patients with refractory angina and no possibilities for coronary revascularization. However, a consistent percentage of patients, ranging from 15 to 30%, reports no clinical benefits after coronary sinus reducer implantation. The reasons for this lack of effectiveness are at present unknown. We suggest here a possible explanation to this phenomenon.

Unexpectedly High Prevalence of Coronary Spastic Angina in Patients With Anderson-Fabry Disease.

BACKGROUND: Although we and others have reported cases of patients with Anderson-Fabry disease (AFD) complicated by coronary spastic angina (CSA), the prevalence of CSA in these patients remains unknown. Methods and Results: We performed the acetylcholine-induced provocation test, according to the Japanese guidelines for the diagnosis and treatment of patients with CSA, in 9 consecutive patients having 5 independent AFD pedigrees. Coronary spasms were provoked in conjunction with symptoms and ECG ischemic changes in 8 of 9 (89%) patients with AFD. CONCLUSIONS: We found an unexpectedly high prevalence of CSA in patients with AFD.

The relationship between epicardial adipose tissue and coronary artery stenosis by sex and menopausal status in patients with suspected angina.

BACKGROUND: Evidence suggests that epicardial adipose tissue (EAT) is closely related to coronary artery stenosis (CAS). However, sexual dimorphism may be present in adipose tissue, and its influence on CAS between men and women is controversial. We assessed the relationship between EAT and CAS by sex and menopausal status in patients with suspected angina. METHODS: Six hundred twenty-eight consecutive patients (men/women n = 257/371; mean age = 59.9 ± 10.2 years) who had chest pain for angina and underwent coronary angiography were included. CAS was defined as > 50% luminal narrowing of at least one epicardial coronary artery. EAT thickness was measured by transthoracic echocardiography. RESULTS: Of the 628 patients, 52.1% (n = 134) of men and 35.3% (n = 131) of women had CAS. The mean EAT thickness was not different between men and women and was larger in patients with CAS (8.04 ± 2.39 vs 6.58 ± 1.88 mm, P < 0.001). EAT thickness was independently associated with CAS in both sexes (P < 0.001). The odds ratio (OR) of EAT for the presence of CAS was higher in men (OR = 1.43, 95% confidence interval [CI] 1.21-1.69) than in women (OR = 1.24, 95% CI 1.10-1.40). EAT thickness was larger in postmenopausal women than in premenopausal women (7.59 ± 2.25 vs 5.80 ± 1.57 mm, P < 0.001) and was independently related with CAS (OR = 1.24, 95% CI 1.09-1.41). This was not the case in premenopausal women. CONCLUSION: In patients with suspected angina, an increase in EAT thickness was independently related to the presence of CAS in both men and women, with it being stronger in men. According to menopausal status in women, EAT thickness is significantly associated with CAS only in postmenopausal women.

Linking cell function with perfusion: insights from the transcatheter delivery of bone marrow-derived CD133+ cells in ischemic refractory cardiomyopathy trial (RECARDIO).

BACKGROUND: Cell therapy with bone marrow (BM)-derived progenitors has emerged as a promising therapeutic for refractory angina (RA) patients. In the present study, we evaluated the safety and preliminary efficacy of transcatheter delivery of autologous BM-derived advanced therapy medicinal product CD133+ cells (ATMP-CD133) in RA patients, correlating perfusion outcome with cell function. METHODS: In the phase I "Endocavitary Injection of Bone Marrow Derived CD133+ Cells in Ischemic Refractory Cardiomyopathy" (RECARDIO) trial, a total of 10 patients with left ventricular (LV) dysfunction (ejection fraction ≤ 45%) and evidence of reversible ischemia, as assessed by single-photon emission computed tomography (SPECT), underwent BM aspiration and fluoroscopy-based percutaneous endomyocardial delivery of ATMP-CD133. Patients were evaluated at 6 and 12 months for safety and preliminary efficacy endpoints. ATMP-CD133 samples were used for in vitro correlations. RESULTS: Patients were treated safely with a mean number of 6.57 ± 3.45 ×  106 ATMP-CD133. At 6-month follow-up, myocardial perfusion at SPECT was significantly ameliorated in terms of changes in summed stress (from 18.2 ± 8.6 to 13.8 ± 7.8, p = 0.05) and difference scores (from 12.0 ± 5.3 to 6.1 ± 4.0, p = 0.02) and number of segments with inducible ischemia (from 7.3 ± 2.2 to 4.0 ± 2.7, p = 0.003). Similarly, Canadian Cardiovascular Society and New York Heart Association classes significantly improved at follow-up vs baseline (p ≤ 0.001 and p = 0.007, respectively). Changes in summed stress score changes positively correlated with ATMP-CD133 release of proangiogenic cytokines HGF and PDGF-bb (r = 0.80, p = 0.009 and r = 0.77, p = 0.01, respectively) and negatively with the proinflammatory cytokines RANTES (r = - 0.79, p = 0.01) and IL-6 (r = - 0.76, p = 0.02). CONCLUSION: Results of the RECARDIO trial suggested safety and efficacy in terms of clinical and perfusion outcomes in patients with RA and LV dysfunction. The observed link between myocardial perfusion improvements and ATMP-CD133 secretome may represent a proof of concept for further mechanistic investigations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02059681 . Registered 11 February 2014.

Accelerated collagen turnover in women with angina pectoris without obstructive coronary artery disease: An iPOWER substudy.

Aim Collagens are major cardiac extracellular matrix components, known to be actively remodelled and accumulated during diffuse myocardial fibrosis. We evaluated whether accelerated collagen turnover described by neo-epitope biomarkers reflecting collagen formation and degradation separates patients with diffuse myocardial fibrosis from asymptomatic controls. Methods and results Seventy-one women with angina pectoris without significant coronary artery disease assessed by invasive coronary angiogram were included. Competitive enzyme-linked immunosorbent assays (ELISAs) measuring circulating protein fragments in serum assessed the formation and degradation of collagen type III (Pro-C3, C3M and C3C), IV (P4NP7S and C4M), V (Pro-C5 and C5M) and VI (Pro-C6 and C6M), and degradation of collagen type I (C1M). Serum samples from 32 age-matched asymptomatic women were included as controls. Symptomatic women presented significantly elevated levels of Pro-C6, C3C, C3M, C4M and C8-C ( p < 0.0001-0.0058) and significantly decreased levels of Pro-C3, C5M and C6M ( p < 0.0001-0.041), reflecting accelerated collagen turnover and an imbalanced collagen formation and degradation compared to controls. Cardiac magnetic resonance T1 mapping was performed to determine extracellular volume fraction and thus diffuse myocardial fibrosis. A significant association was identified between C5M and extracellular volume fraction by cardiac magnetic resonance ( p = 0.01). Conclusion Women with angina pectoris, but without significant obstructive coronary artery disease, showed an imbalanced collagen turnover compared to asymptomatic controls. The examined biomarkers are tools to monitor active collagen remodelling in patients with angina pectoris, in risk of developing myocardial fibrosis.

Characterization of high-intensity plaques on noncontrast T1-weighted magnetic resonance imaging by coronary angioscopy.

BACKGROUND: A recent study showed that coronary high-intensity plaques (HIPs) visualized by noncontrast T1-weighted imaging (T1WI) in cardiac magnetic resonance were associated with coronary events. We used coronary angioscopy to analyze HIP plaque morphology. METHODS AND RESULTS: A total 17 lesions from 17 patients with stable or unstable angina pectoris were evaluated at the culprit lesion by noncontrast T1WI using 1.5-T magnetic resonance; of them, nine (53%) were HIPs and eight (47%) were non-HIPs, and all were analyzed by coronary angioscopy. We assessed the existence of thrombus and plaque yellow color grade (YG). YG was assessed visually according to a four-grade scale: 0, white; 1, light yellow; 2, yellow; 3, intense yellow. The frequency of thrombus was significantly higher in HIPs than in non-HIPs (89% vs. 25%, respectively; p=0.007). YG was significantly more frequent in HIPs than in non-HIPs (2.2±0.4 vs. 0.7±0.7, respectively; p=0.01). CONCLUSIONS: These data indicated that HIPs on noncontrast T1WI were associated with the presence of high-grade yellow plaque with thrombus.

Relationship between the Level of Circulating CD45+ Platelets and Development of Restenosis after Implantation of Drug-Eluting Stents to Patients with Coronary Heart Disease.

The study was carried out in 126 patients with stable angina pectoris, who underwent elective coronary artery stenting with drug-eluting stents and follow-up angiography within 6-12 months thereafter. Five significant risk factors of restenosis were identified by binary comparisons of different variables. The logistic regression equation that included the level of CD45-positive platelets, diabetes, small vessel stenting, number of simultaneously implanted stents in one patient, and lesion length demonstrates the highest level of prediction of in-stent restenosis (OR=22.8; p<0.001). ROC-analysis demonstrated high prognostic value of the logit model (area under ROC curve 0.87, p<0.001). The data suggest that a close relationship exists between the development of restenosis and the level of circulating CD45+ platelets.

Serum Cytokine Profile in Relation to the Severity of Coronary Artery Disease.

Objectives. To investigate the potential association of a set of serum cytokines with the severity of coronary artery disease (CAD). Methods. A total of 201 patients who underwent coronary angiography for chest discomfort were enrolled. The concentrations of serum IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, IL-9, and IL-17 were determined by xMAP multiplex technology. The CAD severity was assessed by Gensini score (GS). Results. The serum levels of TNF-α, IL-6, IL-9, IL-10, and IL-17 were significantly higher in high GS group (GS ≥ 38.5) than those in low GS group (GS < 38.5). Positive correlations were also found between these cytokines and the severity of CAD. After adjustment for other associated factors, three serum cytokines (IL-6, IL-9, and IL-17) and two clinical risk factors (creatinine and LDL-C) were identified as the independent predictors of increased severity of CAD. ROC curve analysis revealed that the logistic regression risk prediction model had a good performance on predicting CAD severity. Conclusions. Combinatorial analysis of serum cytokines (IL-6, IL-9, and IL-17) with clinical risk factors (creatinine and LDL-C) may contribute to the evaluation of the severity of CAD and may help guide the risk stratification of angina patients, especially in primary health facilities and in the catheter lab resource-limited settings.

Coronary microvascular function and myocardial fibrosis in women with angina pectoris and no obstructive coronary artery disease: the iPOWER study.

BACKGROUND: Even in absence of obstructive coronary artery disease women with angina pectoris have a poor prognosis possibly due to coronary microvascular disease. Coronary microvascular disease can be assessed by transthoracic Doppler echocardiography measuring coronary flow velocity reserve (CFVR) and by positron emission tomography measuring myocardial blood flow reserve (MBFR). Diffuse myocardial fibrosis can be assessed by cardiovascular magnetic resonance (CMR) T1 mapping. We hypothesized that coronary microvascular disease is associated with diffuse myocardial fibrosis. METHODS: Women with angina, a clinically indicated coronary angiogram with <50 % stenosis and no diabetes were included. CFVR was measured using dipyridamole (0.84 mg/kg) and MBFR using adenosine (0.84 mg/kg). Focal fibrosis was assessed by 1.5 T CMR late gadolinium enhancement (0.1 mmol/kg) and diffuse myocardial fibrosis by T1 mapping using a modified Look-Locker pulse sequence measuring T1 and extracellular volume fraction (ECV). RESULTS: CFVR and CMR were performed in 64 women, mean (SD) age 62.5 (8.3) years. MBFR was performed in a subgroup of 54 (84 %) of these women. Mean native T1 was 1023 (86) and ECV (%) was 33.7 (3.5); none had focal fibrosis. Median (IQR) CFVR was 2.3 (1.9; 2.7), 23 (36 %) had CFVR < 2 indicating coronary microvascular disease, and median MBFR was 2.7 (2.2; 3.0) and 19 (35 %) had a MBFR value below 2.5. No significant correlations were found between CFVR and ECV or native T1 (R 2 = 0.02; p = 0.27 and R 2 = 0.004; p = 0.61, respectively). There were also no correlations between MBFR and ECV or native T1 (R 2 = 0.1; p = 0.13 and R 2 = 0.004, p = 0.64, respectively). CFVR and MBFR were correlated to hypertension and heart rate. CONCLUSION: In women with angina and no obstructive coronary artery disease we found no association between measures of coronary microvascular disease and myocardial fibrosis, suggesting that myocardial ischemia induced by coronary microvascular disease does not elicit myocardial fibrosis in this population. The examined parameters seem to provide independent information about myocardial and coronary disease.

Clinical Therapeutic Effects of Aspirin in Combination with Fufang Danshen Diwan, a Traditional Chinese Medicine Formula, on Coronary Heart Disease: A Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: Coronary heart disease is characterized by vascular stenosis or occlusion resulting in myocardial ischemia, hypoxia and necrosis. In China, the combination of aspirin and Fufang Danshen Diwan (FDD), a traditional Chinese medicine formula, has been suggested in the treatment of coronary heart disease. There have been several studies comparing the effectiveness of aspirin alone and in combination with FDD to treat coronary artery disease; however, it remains unclear whether combined aspirin therapy is superior. This study was thus designed to clarify this issue through a systematic review and meta-analysis. METHODS: Databases including PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) database, Wanfang Data and VIP Information were searched. Papers were reviewed systematically by two researchers and analyzed using Cochrane software Revman 5.1. RESULTS: Fourteen randomized controlled trials enrolling 1367 subjects were included. Meta-analyses revealed that aspirin in combination with FDD was significantly more effective at alleviating angina pectoris and improving electrocardiogram (ECG) results relative to aspirin therapy alone, reflected by the summary effects for the clinical markedly effective (OR = 2.45; 95% CI 1.95-3.08) and the total effective (OR = 3.92; 95% CI 2.87-5.36) rates. In addition, combined aspirin and FDD was significantly more efficacious than aspirin monotherapy at improving blood lipid levels, as indicated by the following outcomes: 1) reduction of TC level (SMD -1.12; 95% CI -1.49 to -0.76); 2) reduction of TG level (SMD -0.94; 95% CI -1.15 to -0.74); 3) reduction of LDL level (SMD -0.68; 95% CI -0.88 to -0.48); and 4) improvement of HDL level (SMD 0.52; 95% CI 0.04 to 0.99 ). No serious adverse events were reported in any of the included trials. CONCLUSION: The present meta-analysis demonstrated that aspirin in combination with FDD was more effective than aspirin alone for treating coronary heart disease. More full-scale randomized clinical trials with reliable designs are recommended to further evaluate the clinical benefits and long-term effectiveness of FDD for the treatment of coronary heart disease.

Medication Adherence Patterns after Hospitalization for Coronary Heart Disease. A Population-Based Study Using Electronic Records and Group-Based Trajectory Models.

OBJECTIVE: To identify adherence patterns over time and their predictors for evidence-based medications used after hospitalization for coronary heart disease (CHD). PATIENTS AND METHODS: We built a population-based retrospective cohort of all patients discharged after hospitalization for CHD from public hospitals in the Valencia region (Spain) during 2008 (n = 7462). From this initial cohort, we created 4 subcohorts with at least one prescription (filled or not) from each therapeutic group (antiplatelet, beta-blockers, ACEI/ARB, statins) within the first 3 months after discharge. Monthly adherence was defined as having ≥24 days covered out of 30, leading to a repeated binary outcome measure. We assessed the membership to trajectory groups of adherence using group-based trajectory models. We also analyzed predictors of the different adherence patterns using multinomial logistic regression. RESULTS: We identified a maximum of 5 different adherence patterns: 1) Nearly-always adherent patients; 2) An early gap in adherence with a later recovery; 3) Brief gaps in medication use or occasional users; 4) A slow decline in adherence; and 5) A fast decline. These patterns represented variable proportions of patients, the descending trajectories being more frequent for the beta-blocker and ACEI/ARB cohorts (16% and 17%, respectively) than the antiplatelet and statin cohorts (10% and 8%, respectively). Predictors of poor or intermediate adherence patterns were having a main diagnosis of unstable angina or other forms of CHD vs. AMI in the index hospitalization, being born outside Spain, requiring copayment or being older. CONCLUSION: Distinct adherence patterns over time and their predictors were identified. This may be a useful approach for targeting improvement interventions in patients with poor adherence patterns.

[THE CONTENT OF ELECTROLYTES IN DIFFERENT BIOLOGICAL MEDIUMS UNDER ACUTE CORONARY SYNDROME].

The sampling of study included 172 patients with ischemic heart disease: 146 with acute coronary syndrome, including myocardial infarction (88 patients) and unstable stenocardia (58 patients); 26 patients with stable stenocardia functional class II-III. At the 1-3 day of hospitalization blood was taken of cubital vein. The mixed unstimulated saliva was selected. In both of them conte of calcium, sodium and potassium was tested (mmol/l). Under acute coronary syndrome, in blood content of calcium was 2. sodium--139.6 and potassium--4.5 i.e. the content was lower than in case of stable stenocardia (2.4; 139.8; 4.7 correspondingl In saliva under acute coronary syndrome higher content of calcium (1.05) and potassium (34.66) and lower content of sodiu (25.42) was established in comparison with stable stenocardia (0.81; 33.7; 28.08 correspondingly). The distribution coefficien (blood/saliva) of calcium, sodium and potassium were higher under myocardium infarction than under unstable stenocardia at uncomplicated course of acute coronary syndrome.