Chronic Coronary Disease Research Articles

Causes of cardiovascular and noncardiovascular death in the ISCHEMIA trial

The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches trial demonstrated no overall difference in the composite primary endpoint and the secondary endpoints of cardiovascular (CV) death/myocardial infarction or all-cause mortality between an initial invasive or conservative strategy among participants with chronic coronary disease and moderate or severe myocardial ischemia. Detailed cause-specific death analyses have not been reported. We compared overall and cause-specific death rates by treatment group using Cox models with adjustment for pre-specified baseline covariates. Cause of death was adjudicated by an independent Clinical Events Committee as CV, non-CV, and undetermined. We evaluated the association of risk factors and treatment strategy with cause of death. Four-year cumulative incidence rates for CV death were similar between invasive and conservative strategies (2.6% vs 3.0%; hazard ratio [HR] 0.98; 95% CI [0.70-1.38]), but non-CV death rates were higher in the invasive strategy (3.3% vs 2.1%; HR 1.45 [1.00-2.09]). Overall, 13% of deaths were attributed to undetermined causes (38/289). Fewer undetermined deaths (0.6% vs 1.3%; HR 0.48 [0.24-0.95]) and more malignancy deaths (2.0% vs 0.8%; HR 2.11 [1.23-3.60]) occurred in the invasive strategy than in the conservative strategy. In International Study of Comparative Health Effectiveness with Medical and Invasive Approaches, all-cause and CV death rates were similar between treatment strategies. The observation of fewer undetermined deaths and more malignancy deaths in the invasive strategy remains unexplained. These findings should be interpreted with caution in the context of prior studies and the overall trial results.

Updates in the management of valvular heart disease, according to ESC 2021 Guidelines

Valvular heart diseases are encountered more and more often in our professional activity. Their prevalence in recent years has led to an increased concern regarding these path­o­logies. Today, degenerative aortic stenosis is the most frequent cardiovascular disease, after high blood pressure and chronic coronary disease (in Europe and North America). In 2017, a complex guide for the management of valvular heart disease (VHD) was published. But since 2017, new in­for­ma­tion, new studies, new epidemiological data and new recommendations have emerged for these pathologies. All these realities make the actualization and revision of the guide for the management of VHD imperative. This new do­cu­ment focuses on the definition of “Heart Team” and “Heart Valve Centre”, as centers of excellence that can offer ma­xi­mum chances to these patients. Decision-making in VHD involves accurate diagnosis, timing of intervention, risk as­ses­sment and, based on these, the selection of the most sui­table type of intervention.

Ankle-brachial index: more than a diagnostic test?

The ankle-brachial index (ABI) is the relationship between the systolic blood pressure taken at the ankle level and the brachial artery. A pathological ABI (<0.90 or >1.40) indicates the presence of peripheral artery disease (PAD). Many studies indicate the great utility of this test in the diagnosis of PAD due to its ease of use, reproducibility, low cost, and high cost-effectiveness. This evaluation can be directly correlated with cardiovascular morbidity and mortality; however, it has recently been confirmed that a low ABI can be a predictor of major cardiovascular events, as it is related to diabetes mellitus, chronic coronary disease, stroke, and more. The objective of this work was to review the current evidence on the importance of ABI in the diagnosis of PAD and its main role as a predictor of cardiovascular morbidity and mortality.

Monoterapia com inibidores dos receptores P2Y12 em pacientes tratados por meio de intervenção coronária percutânea

Since the mid-1990s, the dual antiplatelet therapy, consisting of the association between acetylsalicylic acid and a platelet P2Y12 receptor inhibitor, is the core of thrombosis prevention after coronary stent implantation, regardless of the models used. It is also used to prevent the occurrence of atherothrombotic events in the late phase after the intervention. The clinical presentation of coronary artery disease influences the duration of dual therapy, which tends to be longer in treated cases of acute coronary syndrome (usually for one year), when compared to cases of chronic coronary disease (often for up to 6 months). After this period, the P2Y12 inhibitor is usually discontinued, and monotherapy with aspirin is maintained. However, in the last two decades, it has been observed that prolonged use of two associated antiplatelet agents predisposes treated cases to bleeding complications, with potentially severe consequences – including increased mortality. Thus, alternatives that minimize this risk have been considered and evaluated, such as early discontinuation of acetylsalicylic acid (between 1 and 3 months after discharge), or the so-called monotherapy with P2Y12 inhibitors, aiming to reduce bleeding without compromising prevention of ischemic events. In the last decade, a series of randomized clinical trials evaluated this hypothesis, generally resulting in reduced bleeding complications, although not necessarily of those classified as major, with no significant increase in the most relevant cardiovascular events. This review discusses the main results of these clinical trials and their potential clinical implications for routine cardiology practice.

Abstract 9515: Heterogeneity of Benefit on Quality of Life With an Invasive versus Conservative Strategy for Chronic Coronary Disease. Results From the ISCHEMIA Trial

Background: The ISCHEMIA trial recently showed that, on average, patients with chronic coronary disease (CCD) and at least moderate ischemia randomized to an invasive strategy (INV) reported less angina and better quality of life (QOL) than those treated conservatively (CON)—an effect sustained through follow-up. To better support shared decision-making for individual patients, we explored the heterogeneity of treatment benefit of the INV vs CON strategy within the ISCHEMIA trial. Methods: Disease-specific QOL was assessed with the Seattle Angina Questionnaire (SAQ; scores range 0-100, higher=less angina/better QOL). An ordinal (proportional odds) model for 1-year SAQ summary score (SAQ SS) produced estimates of the odds of better QOL with randomization to INV vs CON, with potential heterogeneity of treatment benefit explored via interactions between patient factors and treatment. The final model included both significant interactions (accounting for multiple testing) and main effects. Results: Among 4617 patients with CCD from 37 countries randomized to INV vs CON treatment (mean age 64 ± 10 y, 23% women, 40% diabetes), mean SAQ SS was 74.1 ± 18.9 at baseline and 85.7 ± 15.6 at 1 year (p&lt;0.001). Patients with lower baseline SAQ SS (i.e., more angina) and younger patients derived greater symptomatic treatment benefit from INV management (model-based interaction p=0.005 and p=0.004, respectively; Figure). No other patient factor was associated with a differential treatment effect. In the final model, female sex and diabetes were also associated with worse 1-year QOL, independent of treatment. Conclusion: Using data from a large multinational randomized trial, we found that younger patients and those with more angina at baseline derived greater QOL benefit from INV management. As the primary benefit of revascularization in CCD is symptom improvement, this model could be used to better inform individual patient’s decision-making for initial treatment.

Abstract 13154: Association of Serial Health Status Measurements With Clinical Events: Insights From the ISCHEMIA Trial

Introduction: The Seattle Angina Questionnaire (SAQ), a disease-specific health status measure, has been shown to predict future clinical outcomes in patients with chronic coronary disease (CCD) at a single point in time. The prognostic value of serial SAQ scores in patients with CCD is unknown. Methods: Serial assessments of the 7-item SAQ were obtained in the ISCHEMIA trial of patients with CCD and moderate/severe ischemia. Using Cox regression, we examined the association of baseline and 3-month SAQ-7 Summary Scores (SAQ7-SS) with CV death, MI or unstable angina hospitalization over a 12 month period (between 3 and 15 months after randomization) in patients randomized to conservative treatment. We fit several models including: (a) baseline score only; (b) 3-month score only; (c) 3-month change only; (d) baseline and 3-month score; (e) 3-month change and score. Results: The mean age was 64.3 years in 2095 patients randomized to conservative care with SAQ scores at 1 and 3 months; 78% were men. Twelve-month event rates were 3.3% overall; 2.9% with a 3-month SAQ7-SS ≥75, and 6.9% in those with 3-month scores &lt;50. In unadjusted analyses, higher scores at baseline, 3 months, and greater 3-month improvement were associated with fewer clinical events (Figure 1a). In landmark analyses combining serial scores, neither baseline nor change were significant after adjustment for 3-month score (Figures 1b and 1c). Conclusions: We found that the most recent SAQ score was more predictive of subsequent clinical events than prior scores or changes. Following patients’ health status not only provides an assessment of their current angina control, but also a continuously updatable insight into their risk for subsequent cardiac events.

Abstract 12761: Association of Medical Non-Adherence to Health Status Outcomes in the ISCHEMIA Trial

Introduction: In the ISCHEMIA trial, participants managed invasively (INV; guideline-directed medical therapy [GDMT] + angiography ± revascularization) had better health status outcomes than those managed conservatively (CON; GDMT alone). It is unknown whether adherence to prescribed medications affects health status outcomes in chronic coronary disease (CCD). Hypothesis: Patient-reported medication non-adherence more adversely impacts health status outcomes in those treated with a CON, but not an INV, strategy. Methods: Self-reported adherence was assessed at randomization with a modified Morisky-Green-Levine medication adherence measure and patients were dichotomized into adherent (never skipping meds) and non-adherent (occasionally skipping meds). Twelve-month health status outcomes were assessed with the 7-item Seattle Angina Questionnaire (SAQ) Summary Score (SS; range 0-100, higher = better) using adjusted mixed effects cumulative probability models within a Bayesian framework to estimate differences between adherent and non-adherent patients, stratified by study arm. Results: Among 4480 randomized patients in the SAQ cohort, 1245 (27.8%) reported non-adherence at baseline. These patients had worse SAQ scores at baseline (CON: 72.9 ± 19.3 vs. 75.6 ± 18.4; INV: 71.0 ± 19.8 vs. 74.2 ± 18.7) and follow-up (CON: 81.2 ± 18.3 vs. 85.4 ± 15.0; INV: 84.3 ± 17.4 vs. 88.2 ± 13.9). The Figure shows similar posterior distributions of better SAQ scores with adherence in both arms (Mean difference = 1.63 (95% CrI 0.33, 2.89) in CON; 1.93 (95% CrI 0.80, 3.06) in INV). Conclusions: Medication non-adherence—as was reported in over 1 in 4 patients—was associated with worse 12-month health status, an effect that was similar in CON and INV strategies. While causation cannot be established, improving adherence may improve health status outcomes in CCD, regardless of treatment strategy.

Myocardial injury in patients with SARS-CoV-2 pneumonia: Pivotal role of inflammation in COVID-19.

AimsInfection by SARS‐CoV‐2 may result in a systemic disease and a proportion of patients ranging 15%–44% experienced cardiac injury (CI) diagnosed by abnormal troponin levels. The aim of the present study was to analyse the clinical characteristics of a large series of hospitalized patients for COVID‐19 in order to identify predisposing and/or protective factors of CI and the outcome.Methods and resultsThis is an observational, retrospective study on patients hospitalized in two Italian centres (San Raffaele Hospital and Cremona Hospital) for COVID‐19 and at least one high‐sensitivity cardiac troponin (hs‐cTnt) measurement during hospitalization. CI was defined if at least one hs‐cTnt value was above the 99th percentile. The primary end‐point was the occurrence of CI during hospitalization.We included 750 patients (median age 67, IQR 56–77 years; 69% males), of whom 46.9% had history of hypertension, 14.7% of chronic coronary disease and 22.3% of chronic kidney disease (CKD). Abnormal troponin levels (median troponin 74, IQR 34–147 ng/l) were detected in 390 patients (52%) during the hospitalization.At multivariable analysis age, CKD, cancer, C‐reactive protein (CRP) levels were independently associated with CI. Independent predictors of very high troponin levels were chronic kidney disease and CRP levels. Patients with CI showed higher rate of all‐cause mortality (40.0% vs. 9.1%, p = 0.001) compared to those without CI.ConclusionThis large, multicentre Italian study confirmed the high prevalence of CI and its prognostic role in hospitalized patients with COVID‐19, highlighting the leading role of systemic inflammation for the occurrence of CI.

12-month post-trial follow-up of participants in the Australian arm of the second low-dose colchicine trial

Abstract Background In the Australian arm of the LoDoCo2 trial, colchicine 0.5mg daily compared with placebo markedly reduced the risk of cardiovascular (CV) events in patients with chronic coronary disease (2.0 vs 3.9 events per 100 person years, HR 0.51; 95% CI 0.39–0.67). The purpose of this analysis was to explore CV and non-CV outcomes in the Australian cohort out to one year after cessation of trial medication. Methods Information was collected on all potential CV events and non-CV deaths as well as a range of other co-morbidities. All CV events were blindly adjudicated. The analysis examined the primary outcome (a composite of CV death, myocardial infarction, ischemic stroke, and unscheduled revascularization) and non-CV deaths by initial randomized treatment from the beginning of the trial up until one year after cessation of trial medication. A landmark analysis was then used to examine these outcomes from the date of last contact during the trial until one year after cessation of trial medication. Results The clinical status was confirmed in 1819/1824 (99.7%) participants who were alive at the end of the trial, and in 100% of those participants still taking trial medication at the end of the trial. During post-trial follow up, 515 patients (28.2%) were taking non-study colchicine, including 278 (30.5%) originally randomized to colchicine and 237 (25.9%) randomized to placebo. Over the entire follow-up period that included the 12-month period after the trial medication was ceased, the effect of prior exposure to colchicine on the primary CV outcome was still evident (2.2 vs 3.8 events per 100 person years, HR 0.58; 95% CI 0.45–0.74), however no post-trial CV benefit were apparent in the landmark analysis (3.3 vs 3.4 events per 100 person years, HR 0.97; 95% CI 0.56–0.1.69). Over the entire course of follow-up the incidence of new cancer (7.9% vs 7.2% RR 0.91; 95% CI 0.66–1.25) and non-CV death (0.9 vs 0.6 events per 100 person years, HR 1.44; 95% CI 0.92–2.27) was no different in the treatment groups. Conclusion Although the CV benefits of colchicine treatment that emerged during the trial were still evident in the year after stopping study treatment, no additional CV benefit accrued after it was ceased. These data suggest that colchicine should be continued long-term to maximize its CV benefits. Funding Acknowledgement Type of funding sources: None.

Predictive value of cardiac troponin increase after percutaneous coronary intervention: is it just a marker of disease complexity?

Abstract Background/Introduction Peri-procedural myocardial infarction (MI) following percutaneous coronary intervention (PCI) is supposed to have an impact on outcome after PCI for stable coronary disease, but the rate of this event is highly dependent on their definitions. Most of the recently proposed definitions are based on cardiac troponin (hs-cTn) rise. Purpose The purpose of this analysis is to explore the impact of hs-cTn increase on mortality and cardiac events after PCI for chronic coronary disease with baseline normal value of hs-cTn. Methods e-ULTIMASTER is a large, all-comers registry that enrolled 37,198 patients worldwide who underwent PCI with a thin strut, cobalt chromium sirolimus-eluting stent. Risk-based monitoring was performed and all primary endpoint related events were adjudicated. Clinical follow-up was performed at 3 months and 1 year, with primary endpoint of target lesion failure (TLF) at 1 year. For this analysis, we selected patients with stable angina, silent ischemia, or unstable angina with normal hs-cTn values at baseline. We defined the cut-off value of hs-cTn level as the following: &amp;lt;10, 10–35, ≥35 upper limit of normal (ULN). To adjust for differences in baseline characteristics, a propensity analysis (inverse probability of treatment weights, IPTW) was done. Picture 1 shows variables included in the propensity score and differences between the groups (cTn&amp;lt;10 vs cTn 10–35 and cTn&amp;lt;10 vs cTn≥35) before and after matching. Results The number of patients in each subgroup is: hs-cTn&amp;lt;10 (n=3178), 10–35 (n=492), ≥35 (n=303). The mean age of each subgroup is respectively: 66.2; 68.1, 66.6 years (p&amp;lt;0.01). Across the three hs-cTn level groups, many baseline patient characteristics were similar but several lesion and procedure characteristics were significantly different across the three groups including bifurcation lesions, calcification, N of lesions treated, N of stents implanted, total stent length and procedural complications. The unadjusted and adjusted rates of 1-year clinical outcomes are presented in picture 2. All-cause or cardiac death were not increased in cTn≥35 group while there was a trend towards higher target lesion revascularization (TLR) and significantly higher stent thrombosis, majority of which (75% and 91% respectively) occurred during index hospitalization. There was a significantly higher rate of spontaneous MI in both groups with elevated hs-cTn. Conclusion Hs-cTn rise above 35 x ULN was not associated with cardiac or all-cause 1-year mortality. Significantly higher stent thrombosis and a trend towards higher TLR, observed in this group at 1-year, reflect procedure complications, based on the timing of event. When excluding peri-procedural MI in the matched analysis of outcomes, a significantly higher rate of spontaneous MI was observed in both groups with hs-cTn increase. The findings of this analysis suggest that hs-cTn rise is a marker of patient/lesion complexity. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Terumo Picture 1. Baseline variables before/after matchingPicture 2. 1-year clinical outcomes

Clinical features of familial hypercholesterolaemia in children and adults – the PMMHRI Registry

Abstract Background Familial hypercholesterolaemia (FH) affects approximately 150,000 people in Poland. However, there are many patients still unaware of this diagnosis. On the other hand, it might lead to early cardiovascular mortality and morbidity due to the lifetime exposure to high levels of LDL-C. Therefore, increased awareness of FH is very important. Purpose We aimed to evaluate the clinical features of FH in children and adults based on the preliminary data from the Polish Mother's Memorial Hospital Research Institute (PMMHRI) Registry. Methods The registry of children and adults with FH conducted in PMMHRI (2nd largest, supra-regional hospital in Poland) was established to investigate the clinical characteristics, management and clinical outcomes data of FH patients. All consecutive patients with diagnosed (genetically and/or phenotypically) FH were included in the study. Results Of 103 patients with FH, there were 16 children aged 9±3 and 87 adults aged 41±16; 59% were female. The diagnosis of FH in adults was late – at the mean age of 41 years. Among children with FH, as compared with adults, the levels of highest TC and LDL-C ever were similar. However, children presented higher mean levels of total cholesterol, LDL-C and HDL-C measured at baseline visit (Table). Interestingly there was no difference in BMI between children and adults (Table). Among adults, chronic coronary syndrome was diagnosed in 11.5% patients, from which 5.7% patients had a history of myocardial infarction and 7% patients required revascularization. The prevalence of chronic coronary disease, peripheral artery disease as well as stroke in family history was definitely higher (in 44 patients – 50%, 17 patients – 20% and 22 patients – 25%, respectively). Most of adult patients at baseline visit were prescribed statins (rosuvastatin or atorvastatin). 14 patients (13.6%) declared statin intolerance, most of them complained of muscle pain, 4.6% patients reported hepatic disturbances. The frequency of statin use in children was lower – 56% children were prescribed statin, 19% declared statin intolerance with muscle pain as the side-effect of treatment. Ezetimibe, as a part of combination therapy, was taken by 29% adult patients. PCSK9 inhibitors were prescribed (within drug program) for 11.5% adult patients. Fibrates were prescribed for 13.7% adult patients, the same was for n-3 fatty acids. Conclusions Despite definitely younger age of FH diagnosis children present higher mean levels of LDL cholesterol than adults. Therefore, the lifetime exposure to LDL cholesterol starts at a very young age. As a result, there is a need to the earlier initiation of therapy and strict monitoring of the atherosclerosis progression. On the other hand, late diagnosis of FH in adults is an unmet need, that might be associated with poorer prognosis. Funding Acknowledgement Type of funding sources: None.

Value of magnetocardiography in chronic coronary disease detection: results of multicenter trial

Abstract Background Diagnostic management of patients with chest pain remains a clinical challenge. Magnetocardiography (MCG) is non-invasive evaluation of the magnetic field of the heart that is produced by the electric activity of the myocardium. Previous studies have clearly demonstrated the potential of MCG in coronary artery disease (CAD) detection. The objective of this multicenter trial is the investigation of value of MCG in diagnosis of mild and severe coronary artery disease using novel approach of magnetocardiographic current density vectors (CDV) maps evaluation. Methods This clinical trial was conducted in three GCP accredited institutions under the leadership of a General Hospital in China. The trials were designed for paired experiments with multi-center blind interpretation. Coronary angiography and coronary flow reserve fraction were used as a “gold standard”. In total 133 persons (mean age 59±3,1 years), divided into 3 groups, were examined. The first group (61 subjects) was identified for patients with severe myocardial ischemia and met the criteria for revascularization: degree of coronary artery stenosis is ≥80% or coronary blood flow reserve score ≤0,8. The second group (13 subjects) is patients whose myocardial ischemia is confirmed but has not yet reached the criteria for revascularization: coronary artery stenosis is between 50% and 80%, coronary blood flow reserve score &amp;gt;0,8. The third group (59 subjects) is whom the “gold standard” confirmed that there is no coronary artery disease. This group is called the negative control group. The MCG examination was performed using a 7-channel MCG system located in an unshielded room. Magnetocardiography recordings were taken from 36 positions at rest Based on the magnetic field distribution, set of subsequent current vectors maps were reconstructed with equidistant time step (10 ms) within the ST-T interval. Each of these maps was classified into two categories: normal map or pathological map. This classification is based on the analysis of the of the largest current density vectors direction and dipole or non-dipole structure of the map. Then, portion of pathological CDV maps within the ST-T interval was defined. Based of this portion, each MCG examination was was assigned to one of 3 groups: mild CAD, severe CAD or no CAD. Results The coincidence rate of each group was as follows: coincidence rate of severe CAD – 85,45%, coincidence rate of mild CAD – 77,78%, coincidence rate of control group was 87,10%. Sensitivity 93,75% and specificity 87,10% were achieved, PPS was 88,24%, NPV 93,10%. In terms of likelhood ratio results were as follows: a positive likelhood ratio of 7.27, negative likelhood ratio – 0.07. Conclusion MCG-examination seems to be a reliable method in the diagnosis of chronic severe and mild CAD. Further large-scale studies needed to confirm these findings. Funding Acknowledgement Type of funding sources: None.

Coronary venous therapy to improve microvascular dysfunction

The coronary circulation is a complex system in which vascular resistances are determined by an interplay of forces in at least three compartments: the epicardial, the microvascular, and the venous district. Cardiologists, and particularly interventional cardiologists, normallly place the focus of their attention on diseases of the epicardial coronary circulation as possible causes of coronary syndromes and neglect the importance of the other two compartments of coronary circulation. The study of the coronary microcirculation, an increasingly recognized source of ischemia, has long been disregarded, but is witnessing a revival since the (re-)introduction of diagnostic tools in the better equipped catheterization laboratories. Unfortunately, to date our understanding of coronary microvascular disease remains incomplete and the numerous proposed classifications fail to reflect its complexity. Further, no specific therapy for these disorders is available. The coronary venous circulation is an even more neglected third vascular district. Its role in regulating coronary resistances is almost completely unexplored, but inital evidence suggests that the modulation of venous pressure might help improve coronary perfusion. Coronary sinus interventions are a group of invasive techniques (both surgical and catheter-based) that are designed to treat ischaemic heart disease by increasing coronary venous pressure and therefore redistributing coronary blood flow towards the endocardium. In this review paper, we revise the role of these interventions with particular focus on acute and chronic coronary microvascular disease.

Outcomes of Participants With Diabetes in the ISCHEMIA Trials.

Among patients with diabetes and chronic coronary disease, it is unclear if invasive management improves outcomes when added to medical therapy. The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trials (ie, ISCHEMIA and ISCHEMIA-Chronic Kidney Disease) randomized chronic coronary disease patients to an invasive (medical therapy + angiography and revascularization if feasible) or a conservative approach (medical therapy alone with revascularization if medical therapy failed). Cohorts were combined after no trial-specific effects were observed. Diabetes was defined by history, hemoglobin A1c ≥6.5%, or use of glucose-lowering medication. The primary outcome was all-cause death or myocardial infarction (MI). Heterogeneity of effect of invasive management on death or MI was evaluated using a Bayesian approach to protect against random high or low estimates of treatment effect for patients with versus without diabetes and for diabetes subgroups of clinical (female sex and insulin use) and anatomic features (coronary artery disease severity or left ventricular function). Of 5900 participants with complete baseline data, the median age was 64 years (interquartile range, 57-70), 24% were female, and the median estimated glomerular filtration was 80 mL·min-1·1.73-2 (interquartile range, 64-95). Among the 2553 (43%) of participants with diabetes, the median percent hemoglobin A1c was 7% (interquartile range, 7-8), and 30% were insulin-treated. Participants with diabetes had a 49% increased hazard of death or MI (hazard ratio, 1.49 [95% CI, 1.31-1.70]; P<0.001). At median 3.1-year follow-up the adjusted event-free survival was 0.54 (95% bootstrapped CI, 0.48-0.60) and 0.66 (95% bootstrapped CI, 0.61-0.71) for patients with diabetes versus without diabetes, respectively, with a 12% (95% bootstrapped CI, 4%-20%) absolute decrease in event-free survival among participants with diabetes. Female and male patients with insulin-treated diabetes had an adjusted event-free survival of 0.52 (95% bootstrapped CI, 0.42-0.56) and 0.49 (95% bootstrapped CI, 0.42-0.56), respectively. There was no difference in death or MI between strategies for patients with diabetes versus without diabetes, or for clinical (female sex or insulin use) or anatomic features (coronary artery disease severity or left ventricular function) of patients with diabetes. Despite higher risk for death or MI, chronic coronary disease patients with diabetes did not derive incremental benefit from routine invasive management compared with initial medical therapy alone. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Патогенетична та клінічна спорідненість перебігу цукрового діабету 2-го типу з метаболічним синдромом та хронічною ішемічною хворобою серця

Актуальність. Зростання захворюваності на цукровий діабет (ЦД) при поєднанні з ішемічною хворобою серця (ІХС) на тлі метаболічного синдрому (МС) викликає занепокоєння. Насамперед потребують вдосконалення підходи до своєчасної діагностики з врахуванням конкретного стану даної коморбідної патології, а також вироблення патогенетичної терапії. Мета дослідження — вивчення взаємозв’язку ЦД 2-го типу в компенсованому і декомпенсованому станах на тлі МС із хронічною ІХС. Матеріали та методи. Обстежений 231 пацієнт із МС за відсутності та наявності ЦД 2-го типу та хронічної ІХС. У всіх хворих було ожиріння ІІ–ІІІ ступеня. Визначали рівень кортизолу, пролактину, вільного тироксину, тиреотропного гормона (ТТГ), показники ліпідного спектра та досліджували структурно-функціональний стан міокарда за допомогою ехокардіографії. Результати. В осіб із МС, а також у пацієнтів із компенсованим ЦД 2-го типу на тлі МС виявлено підвищені рівні кортизолу, пролактину в жінок, ТТГ, зміни ліпідного спектра у вигляді високих рівнів тригліцеридів та ліпопротеїнів дуже низької щільності, зрушення показників структурно-функціонального стану міокарда за рахунок збільшення товщини міжшлуночкової перегородки та розміру лівого передсердя. У пацієнтів із МС із декомпенсованим ЦД 2-го типу як за відсутності, так і наявності хронічної ІХС виявлено підвищений рівень кортизолу та пролактину при контрольній величині ТТГ. В обох групах при аналізі ультрасонографічних параметрів спостерігалось збільшення товщини міжшлуночкової перегородки, задньої стінки лівого шлуночка, розміру лівого передсердя. Звертає на себе увагу високий рівень холестерину, ліпопротеїнів низької щільності, тригліцеридів, ліпопротеїнів дуже низької щільності та низький рівень ліпопротеїнів високої щільності в пацієнтів із МС та декомпенсованим ЦД 2-го типу, ускладненим хронічною ІХС, порівняно з пацієнтами з МС з ЦД 2-го типу без хронічної ІХС. Висновки. Установлено патогенетичну та клінічну спорідненість стадій цукрового діабету 2-го типу з метаболічним синдромом та хронічною ішемічною хворобою серця.

Роль щитоподібної залози при метаболічному синдромі та в поєднанні з хронічною ішемічною хворобою серця та цукровим діабетом 2-го типу

Актуальність. Метаболічний синдром (МС), в основі якого лежать порушення ліпідного, вуглеводного обміну та гормонального статусу, зокрема функціонального стану гіпоталамо-гіпофізарної і тиреоїдної систем, є актуальною проблемою ХХІ століття, виступає як критерій тяжкості перебігу цукрового діабету (ЦД) 2-го типу та ішемічної хвороби серця (ІХС). Функціональний стан щитоподібної залози (ЩЗ) при МС дедалі частіше стає об’єктом досліджень багатьох вчених. Доведено, що в регуляції секреції інсуліну важливе місце посідають гормони ЩЗ, відома концепція гіпотиреозіндукованого МС. Субклінічний гіпотиреоз є незалежним фактором ризику атеросклерозу та гострого коронарного синдрому у жінок старшого віку. З огляду на це важливо приділити значну увагу дослідженню ЩЗ при коморбідній патології. Мета дослідження: вивчення функціонального стану щитоподібної залози при метаболічному синдромі та в поєднанні з хронічною ішемічною хворобою серця та цукровим діабетом 2-го типу в стані компенсації та декомпенсації. Матеріали та методи. Обстежено 319 пацієнтів із МС в поєднанні його з хронічною ІХС і ЦД 2-го типу в стані компенсації та декомпенсації. Залежно від наявності чи відсутності поєднаної патології сформовано шість груп пацієнтів із МС. Першу групу становили пацієнти з МС без ускладнень, другу групу — особи з МС та компенсованим ЦД 2-го типу, третю групу — хворі з МС та декомпенсованим ЦД 2-го типу, четверту групу — особи з МС у поєднанні з хронічною ІХС, п’яту групу — хворі з МС у поєднанні з хронічною ІХС та компенсованим ЦД 2-го типу, шосту групу — пацієнти з МС, хронічною ІХС та декомпенсованим ЦД 2-го типу. Пацієнтам визначали рівні тиреотропного гормону (ТТГ), кортизолу, вільного тироксину (вТ4), а також антитіл до тиреоглобуліну і тиреоїдної пероксидази з метою з’ясування функціонального стану ЩЗ і підтвердження її патогенетичної участі в цій комплексній патології. Результати. Для МС без ускладнень, а також для МС із хронічною ІХС і МС з хронічною ІХС та ЦД в стані компенсації властиве збільшення рівня ТТГ. Ці зміни вказують на наявність субклінічного гіпотиреозу, беручи до уваги нормальні рівні вТ4. Зрушення кортизолу при цьому характерні спочатку в сторону його підвищення при МС без ускладнень, з подальшим його зниженням. При МС з хронічною ІХС та декомпенсованому ЦД рівень ТТГ перебуває на рівні контрольної групи, що вказує на нормалізацію функції ЩЗ, з одночасним підвищенням рівня кортизолу. Висновки. Рівні ТТГ та кортизолу є маркерами тяжкості перебігу поєднаної патології (МС з хронічною ІХС та ЦД 2-го типу).

Coronary artery bypass grafting versus stent implantation in patients with chronic coronary syndrome and left main disease: insights from a register throughout Germany

BackgroundRecent randomized controlled trials have sparked debate about the optimal treatment of patients suffering from left main coronary artery disease. The present study analyzes outcomes of left main stenting versus coronary bypass grafting (CABG) in a nationwide registry in patients with chronic coronary syndrome (CCS).MethodsAll cases suffering from CCS and left main coronary artery disease treated either with CABG or stent, were identified within the database of the German bureau of statistics. Logistic or linear regression models were used with 20 baseline patient characteristics as potential confounders to compare both regimens.ResultsIn 2018, 1318 cases with left main stenosis were treated with CABG and 8,920 with stent. Patients assigned for stenting were older (72.58 ± 9.87 vs. 68.63 ± 9.40, p < 0.001) and at higher operative risk, as assessed by logistic EuroSCORE (8.77 ± 8.45 vs. 4.85 ± 4.65, p < 0.001). After risk adjustment, no marked differences in outcomes were found for in-hospital mortality and stroke (risk adjusted odds ratio (aOR) for stent instead of CABG: aOR mortality: 1.08 [95% CI 0.66; 1.78], p = 0.748; aOR stroke: 0.59 [0.27; 1.32], p = 0.199). Stent implantation was associated with a reduced risk of relevant bleeding (aOR 0.38 [0.24; 0.61], p < 0.001), reduced prolonged ventilation time (aOR 0.54 [0.37 0.79], p = 0.002), and postoperative delirium (aOR 0.16 [0.11; 0.22], p < 0.001). Furthermore, stent implantation was associated with shorter hospital stay (− 6.78 days [− 5.86; − 7.71], p < 0.001) and lower costs (− €10,035 [− €11,500; − €8570], p < 0.001).ConclusionLeft main stenting is a safe and effective treatment option for CCS-patients suffering from left main coronary artery disease at reasonable economic cost.Graphic abstractCoronary artery bypass grafting versus stent implantation in patients with chronic coronary syndrome and left main disease: insights from a register throughout Germany. All cases with chronic coronary syndrome and left main stenosis treated in 2018 in Germany either with left main stenting or coronary bypass grafting were extracted from a nation-wide database. In-hospital outcomes were compared after logistic regression analysis.

Risk Factors of SARS-CoV-2 Infection: Global Epidemiological Study.

BackgroundSince the first recognition of the pandemic characteristics of SARS-CoV-2 infection, and before substantial case fatality data were available worldwide, public health agencies warned the public about the increased dangers of SARS-CoV-2 to persons with a variety of underlying physical conditions, many of which are more commonly found in persons over 50 years of age or in certain ethnic groups.ObjectiveTo investigate the statistical rather than the physiological basis in support of the abovementioned warnings, this study examines correlations globally on a nation-by-nation basis between the statistical data concerning COVID-19 fatalities and the statistics of potential comorbidities that may influence the severity of infection.MethodsThis study considers the statistics describing the populations of the 99 countries with the greatest numbers of SARS-CoV-2 infections at the time of the data cutoff. As national compilations of direct measures of immune system strength are not publicly available, the frequency of fatalities in those countries due to a variety of serious diseases is used as a proxy for the susceptibility of those populations to those same diseases.ResultsThe analysis produces plots and calculations of correlations and cross-correlations of COVID-19 case fatality rates and the risks of other potential cofactors. It exposes some reasons that may underlie the degree to which advanced age increases the risk of mortality of infection with SARS-CoV-2. In contrast with the strong influences of comorbidities on the seriousness of consequences of influenzas and their associated pneumonias, the correlations of the same set of risk factors with SARS-CoV-2 infection are considerably weaker. The general characteristics of the observed correlations strengthened through 3 cycles of analysis, starting in September 2020. The strongest correlations were with chronic kidney disease and coronary disease (approximately 0.28 and 0.20, respectively).ConclusionsThis study confirms early clinical observations that infection with SARS-CoV-2 presents an increased risk to persons over the age of 65 years. It does not support the suggestions presented by government agencies early in the pandemic that the risks are much greater for persons with certain common potential comorbidities.

Susceptibility of β-Thalassemia Heterozygotes to COVID-19

Background: β-Thalassemia is the most prevalent single gene blood disorder, while the assessment of its susceptibility to coronavirus disease 2019 (COVID-19) warrants it a pressing biomedical priority. Methods: We studied 255 positive COVID-19 participants unvaccinated against severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2), consecutively recruited during the last trimester of 2020. Patient characteristics including age, sex, current smoking status, atrial fibrillation, chronic respiratory disease, coronary disease, diabetes, neoplasia, hyperlipidemia, hypertension, and β-thalassemia heterozygosity were assessed for COVID-19 severity, length of hospitalization, intensive care unit (ICU) admission and mortality from COVID-19. Results: We assessed patient characteristics associated with clinical symptoms, ICU admission, and mortality from COVID-19. In multivariate analysis, severe-critical COVID-19 was strongly associated with male sex (p = 0.023), increased age (p < 0.001), and β-thalassemia heterozygosity (p = 0.002, OR = 2.89). Regarding the requirement for ICU care, in multivariate analysis there was a statistically significant association with hypertension (p = 0.001, OR = 5.12), while β-thalassemia heterozygosity had no effect (p = 0.508, OR = 1.33). Mortality was linked to male sex (p = 0.036, OR = 2.09), increased age (p < 0.001) and β-thalassemia heterozygosity (p = 0.010, OR = 2.79) in multivariate analysis. It is worth noting that hyperlipidemia reduced mortality from COVID-19 (p = 0.008, OR = 0.38). No statistically significant association of current smoking status with patient characteristics studied was observed. Conclusions: Our pilot observations indicate enhanced mortality of β-thalassemia heterozygotes from COVID-19.

Colchicine reduces extracellular vesicle NLRP3 inflammasome protein levels in chronic coronary disease: A LoDoCo2 biomarker substudy

Background and aimsColchicine reduces the risk of cardiovascular events in patients with coronary disease. Colchicine has broad anti-inflammatory effects and part of the atheroprotective effects have been suggested to be the result of NLRP3 inflammasome inhibition. We studied the effect of colchicine on extracellular vesicle (EV) NLRP3 protein levels and inflammatory markers, high sensitivity-CRP (hs-CRP) and interleukin (IL)-6, in patients with chronic coronary disease. MethodsIn vitro, the NLRP3 inflammasome was stimulated in PMA-differentiated- and undifferentiated THP-1 cells. In vivo, measurements were performed in serum obtained from 278 participants of the LoDoCo2 trial, one year after randomization to colchicine 0.5 mg once daily or placebo. EVs were isolated using precipitation. NLRP3 protein presence in EVs was confirmed using iodixanol density gradient centrifugation. Levels of NLRP3 protein, hs-CRP and IL-6 were measured using ELISA. ResultsIn vitro, NLRP3 inflammasome stimulation showed an increase of EV NLRP3 protein levels.EV NLRP3 protein levels were lower in patients treated with colchicine (median 1.38 ng/mL), compared to placebo (median 1.58 ng/mL) (p = 0.025). No difference was observed in serum NLRP3 protein levels. Serum hs-CRP levels were lower in patients treated with colchicine (median 0.80 mg/L) compared to placebo (median 1.34 mg/L) (p < 0.005). IL-6 levels were lower in patients treated with colchicine (median 2.07 ng/L) compared to placebo (median 2.59 ng/L), although this was not statistically significant (p = 0.076). ConclusionsColchicine leads to a reduction of EV NLRP3 protein levels. This indicates that inhibitory effects on the NLRP3 inflammasome might contribute to the atheroprotective effects of colchicine in coronary disease.