Long-term outcomes of patients with stable coronary disease and chronic kidney dysfunction: 10-year follow-up of the Medicine, Angioplasty, or Surgery Study II Trial.

BACKGROUND: Chronic kidney disease (CKD) is associated with a worse prognosis in patients with stable coronary artery disease (CAD); however, there is limited randomized data on long-term outcomes of CAD therapies in these patients. We evaluated long-term outcomes of CKD patients with CAD who underwent randomized therapy with medical treatment (MT) alone, percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG). METHODS: Baseline estimated glomerular filtration rate (eGFR) was obtained in 611 patients randomized to one of three therapeutic strategies in the Medicine, Angioplasty, or Surgery Study II trial. Patients were categorized in preserved renal function and mild or moderate CKD groups depending on their eGFR (≥90, 89-60 and 59-30 mL/min/1.73 m2, respectively). The primary clinical endpoint, a composite of overall death and myocardial infarction, and its individual components were analyzed using proportional hazards regression (Clinical Trial registration information: http://www.controlled-trials.com. Registration number: ISRCTN66068876). RESULTS: Of 611 patients, 112 (18%) had preserved eGFR, 349 (57%) mild dysfunction and 150 (25%) moderate dysfunction. The primary endpoint occurred in 29.5, 32.4 and 44.7% (P = 0.02) for preserved eGFR, mild CKD and moderate CKD, respectively. Overall mortality incidence was 18.7, 23.8 and 39.3% for preserved eGFR, mild CKD and moderate CKD, respectively (P = 0.001). For preserved eGFR, there was no significant difference in outcomes between therapies. For mild CKD, the primary event rate was 29.4% for PCI, 29.1% for CABG and 41.1% for MT (P = 0.006) [adjusted hazard ratio (HR) = 0.26, 95% confidence interval (CI) 0.07-0.88; P = 0.03 for PCI versus MT; and adjusted HR = 0.48; 95% CI 0.31-0.76; P = 0.002 for CABG versus MT]. We also observed higher mortality rates in the MT group (28.6%) compared with PCI (24.1%) and CABG (19.0%) groups (P = 0.015) among mild CKD subjects (adjusted HR = 0.44, 95% CI 0.25-0.76; P = 0.003 for CABG versus MT; adjusted HR = 0.56, 95% CI 0.07-4.28; P = 0.58 for PCI versus MT). Results were similar with moderate CKD group but did not achieve significance. CONCLUSIONS: Coronary interventional therapy, both PCI and CABG, is associated with lower rates of events compared with MT in mild CKD patients >10 years of follow-up. More study is needed to confirm these benefits in moderate CKD.

Troponin in diabetic patients with and without chronic coronary artery disease.

BACKGROUND: Cardiac-specific troponin detected with the new high-sensitivity assays can be chronically elevated in response to cardiovascular comorbidities and confer important prognostic information, in the absence of unstable coronary syndromes. Both diabetes mellitus and coronary artery disease are known predictors of troponin elevation. It is not known whether diabetic patients with coronary artery disease have different levels of troponin compared with diabetic patients with normal coronary arteries. To investigate this question, we determined the concentrations of a level 1 troponin assay in two groups of diabetic patients: those with multivessel coronary artery disease and those with angiographically normal coronary arteries. METHODS: We studied 95 diabetic patients and compared troponin in serum samples from 50 patients with coronary artery disease (mean age = 63.7, 58 % male) with 45 controls with angiographically normal coronary arteries. Brain natriuretic peptide and the oxidative stress biomarkers myeloperoxidase, nitrotyrosine and oxidized LDL were also determined. RESULTS: Diabetic patients with coronary artery disease had higher levels of troponin than did controls (median values, 12.0 pg/mL (95 % CI:10-16) vs 7.0 pg/mL (95 % CI: 5.9-8.5), respectively; p = 0.0001). The area under the ROC curve for the diagnosis of CAD was 0.712 with a sensitivity of 70 % and a specificity of 66 %. Plasma BNP levels and oxidative stress variables (myeloperoxidase, nitrotyrosine, and oxidized LDL) were not different between the two groups. In a multivariate analysis, gender (p = 0.04), serum glucose (0.03) and Troponin I (p = 0.01) had independent statistical significance. CONCLUSION: Troponin elevation is related to the presence of chronic coronary artery disease in diabetic patients with multiple associated cardiovascular risk factors. Troponin may serve as a biomarker in this high-risk population. TRIAL REGISTRATION: http://www.controlled-trials.com REGISTRATION NUMBER: ISRCTN26970041.

Long-term analysis of left ventricular ejection fraction in patients with stable multivessel coronary disease undergoing medicine, angioplasty or surgery: 10-year follow-up of the MASS II trial.

BACKGROUND: Assuming that coronary interventions, both coronary bypass surgery (CABG) and percutaneous coronary intervention (PCI), are directed to preserve left ventricular function, it is not known whether medical therapy alone (MT) can achieve this protection. Thus, we evaluated the evolution of LV ejection fraction (LVEF) in patients with stable coronary artery disease (CAD) treated by CABG, PCI, or MT as a post hoc analysis of a randomized controlled trial with a follow-up of 10 years. METHODS: Left ventricle ejection fraction was assessed with transthoracic echocardiography in patients with multivessel CAD, participants of the MASS II trial before randomization to CABG, PCI, or MT, and re-evaluated after 10 years of follow-up. RESULTS: Of the 611 patients, 422 were alive after 10.32 ± 1.43 years. Three hundred and fifty had LVEF reassessed: 108 patients from MT, 111 from CABG, and 131 from PCI. There was no difference in LVEF at the beginning (0.61 ± 0.07, 0.61 ± 0.08, 0.61 ± 0.09, respectively, for PCI, CABG, and MT, P = 0.675) or at the end of follow-up (0.56 ± 0.11, 0.55 ± 0.11, 0.55 ± 0.12, P = 0.675), or in the decline of LVEF (reduction delta of -7.2 ± 17.13, -9.08 ± 18.77, and -7.54 ± 22.74). Acute myocardial infarction (AMI) during the follow-up was associated with greater reduction in LVEF. The presence of previous AMI (OR: 2.50, 95% CI: 1.40-4.45; P = 0.0007) and during the follow-up (OR: 2.73, 95% CI: 1.25-5.92; P = 0.005) was associated with development of LVEF <45%. CONCLUSION: Regardless of the therapeutic option applied, LVEF remains preserved in the absence of a major adverse cardiac event after 10 years of follow-up. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Registration number ISRCTN66068876.

Cost-effectiveness analysis for surgical, angioplasty, or medical therapeutics for coronary artery disease: 5-year follow-up of medicine, angioplasty, or surgery study (MASS) II trial.

BACKGROUND: The Second Medicine, Angioplasty, or Surgery Study (MASS II) included patients with multivessel coronary artery disease and normal systolic ventricular function. Patients underwent coronary artery bypass graft surgery (CABG, n=203), percutaneous coronary intervention (PCI, n=205), or medical treatment alone (MT, n=203). This investigation compares the economic outcome at 5-year follow-up of the 3 therapeutic strategies. METHODS AND RESULTS: We analyzed cumulative costs during a 5-year follow-up period. To analyze the cost-effectiveness, adjustment was made on the cumulative costs for average event-free time and angina-free proportion. Respectively, for event-free survival and event plus angina-free survival, MT presented 3.79 quality-adjusted life-years and 2.07 quality-adjusted life-years; PCI presented 3.59 and 2.77 quality-adjusted life-years; and CABG demonstrated 4.4 and 2.81 quality-adjusted life-years. The event-free costs were $9071.00 for MT; $19,967.00 for PCI; and $18,263.00 for CABG. The paired comparison of the event-free costs showed that there was a significant difference favoring MT versus PCI (P<0.01) and versus CABG (P<0.01) and CABG versus PCI (P=0.01). The event-free plus angina-free costs were $16,553.00, $25,831.00, and $24,614.00, respectively. The paired comparison of the event-free plus angina-free costs showed that there was a significant difference favoring MT versus PCI (P=0.04), and versus CABG (P<0.001); there was no difference between CABG and PCI (P>0.05). CONCLUSIONS: In the long-term economic analysis, for the prevention of a composite primary end point, MT was more cost effective than CABG, and CABG was more cost-effective than PCI. CLINICAL TRIAL REGISTRATION INFORMATION: www.controlled-trials.com. REGISTRATION NUMBER: ISRCTN66068876.

Effect of complete revascularization on 10-year survival of patients with stable multivessel coronary artery disease: MASS II trial.

BACKGROUND: The importance of complete revascularization remains unclear and contradictory. This current investigation compares the effect of complete revascularization on 10-year survival of patients with stable multivessel coronary artery disease (CAD) who were randomly assigned to percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG). METHODS AND RESULTS: This is a post hoc analysis of the Second Medicine, Angioplasty, or Surgery Study (MASS II), which is a randomized trial comparing treatments in patients with stable multivessel CAD, and preserved systolic ventricular function. We analyzed patients who underwent surgery (CABG) or stent angioplasty (PCI). The survival free of overall mortality of patients who underwent complete (CR) or incomplete revascularization (IR) was compared. Of the 408 patients randomly assigned to mechanical revascularization, 390 patients (95.6%) underwent the assigned treatment; complete revascularization was achieved in 224 patients (57.4%), 63.8% of those in the CABG group and 36.2% in the PCI group (P=0.001). The IR group had more prior myocardial infarction than the CR group (56.2% × 39.2%, P=0.01). During a 10-year follow-up, the survival free of cardiovascular mortality was significantly different among patients in the 2 groups (CR, 90.6% versus IR, 84.4%; P=0.04). This was mainly driven by an increased cardiovascular specific mortality in individuals with incomplete revascularization submitted to PCI (P=0.05). CONCLUSIONS: Our study suggests that in 10-year follow-up, CR compared with IR was associated with reduced cardiovascular mortality, especially due to a higher increase in cardiovascular-specific mortality in individuals submitted to PCI. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.controlled-trials.com. REGISTRATION NUMBER: ISRCTN66068876.

Impact of diabetes on 10-year outcomes of patients with multivessel coronary artery disease in the Medicine, Angioplasty, or Surgery Study II (MASS II) trial.

INTRODUCTION: Diabetes mellitus is a major cause of coronary artery disease (CAD). Despite improvement in the management of patients with stable CAD, diabetes remains a major cause of increased morbidity and mortality. There is no conclusive evidence that either modality is better than medical therapy alone for the treatment of stable multivessel CAD in patients with diabetes in a very long-term follow-up. Our aim was to compare 3 therapeutic strategies for stable multivessel CAD in a diabetic population and non-diabetic population. METHODS: It was compared medical therapy (MT), percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) in 232 diabetic patients and 379 nondiabetic patients with multivessel CAD. Endpoints evaluated were overall and cardiac mortality. RESULTS: Patients (n = 611) were randomized to CABG (n = 203), PCI (n = 205), or MT (n = 203). In a 10-year follow-up, more deaths occurred among patients with diabetes than among patients without diabetes (P = .001) for overall mortality. In this follow-up, 10-year mortality rates were 32.3% and 23.2% for diabetics and non-diabetics respectively (P = .024). Regarding cardiac mortality, 10-year cardiac mortality rates were 19.4% and 12.7% respectively (P = .031).Considering only diabetic patients and stratifying this population by treatment option, we found mortality rates of 31.3% for PCI, 27.5% for CABG and 37.5% for MT (P = .015 for CABG vs MT) and cardiac mortality rates of 18.8%, 12.5% and 26.1% respectively (P = .005 for CABG vs MT). CONCLUSIONS/INTERPRETATION: Among patients with stable multivessel CAD and preserved left ventricular ejection fraction, the 3 therapeutic regimens had high rates of overall and cardiac-related deaths among diabetic compared with non-diabetic patients. Moreover, better outcomes were observed in diabetic patients undergoing CABG compared to MT in relation to overall and cardiac mortality in a 10-year follow-up.

Hypotheses, rationale, design, and methods for evaluation of ischemic preconditioning assessed by sequential exercise tests in diabetic and non-diabetic patients with stable coronary artery disease--a prospective study.

BACKGROUND: Ischemic preconditioning is a powerful mechanism of myocardial protection and in humans it can be evaluated by sequential exercise tests. Coronary Artery Disease in the presence of diabetes mellitus may be associated with worse outcomes. In addition, some studies have shown that diabetes interferes negatively with the development of ischemic preconditioning. However, it is still unknown whether diabetes may influence the expression of ischemic preconditioning in patients with stable multivessel coronary artery disease. METHODS/DESIGN: This study will include 140 diabetic and non-diabetic patients with chronic, stable coronary artery disease and preserved left ventricular systolic function. The patients will be submitted to two sequential exercise tests with 30-minutes interval between them. Ischemic parameters will be compared between diabetic and non-diabetic patients. Ischemic preconditioning will be considered present when time to 1.0 mm ST-segment deviation is greater in the second of two sequential exercise tests. Exercise tests will be analyzed by two independent cardiologists. DISCUSSION: Ischemic preconditioning was first demonstrated by Murry et al. in dog's hearts. Its work was reproduced by other authors, clearly demonstrating that brief periods of myocardial ischemia followed by reperfusion triggers cardioprotective mechanisms against subsequent and severe ischemia. On the other hand, the demonstration of ischemic preconditioning in humans requires the presence of clinical symptoms or physiological changes difficult to be measured. One methodology largely accepted are the sequential exercise tests, in which, the improvement in the time to 1.0 mm ST depression in the second of two sequential tests is considered manifestation of ischemic preconditioning.Diabetes is an important and independent determinant of clinical prognosis. It's a major risk factor for coronary artery disease. Furthermore, the association of diabetes with stable coronary artery disease imposes worse prognosis, irrespective of treatment strategy. It's still not clearly known the mechanisms responsible by these worse outcomes. Impairment in the mechanisms of ischemic preconditioning may be one major cause of this worse prognosis, but, in the clinical setting, this is not known. The present study aims to evaluate how diabetes mellitus interferes with ischemic preconditioning in patients with stable, multivessel coronary artery disease and preserved systolic ventricular function.

Chronic troponin elevation assessed by myocardial T1 mapping in patients with stable coronary artery disease.

BACKGROUND: Cardiac troponin detected with sensitive assays can be chronically elevated, in the absence of unstable coronary syndromes. In patients with chronic coronary artery disease, clinically silent ischemic episodes may cause chronic troponin release. T1 mapping is a cardiovascular magnetic resonance technique useful in quantitative cardiac tissue characterization. We selected patients with anatomically and functionally normal hearts to investigate associations between chronic troponin release and myocardial tissue characteristics assessed by T1 mapping. METHODS: We investigated the relationship between cardiac troponin I concentrations and cardiovascular magnetic resonance T1 mapping parameters in patients with stable coronary artery disease enrolled in MASS V study before elective revascularization. Participants had no previous myocardial infarction, negative late gadolinium enhancement, normal left ventricular function, chamber dimensions and wall thickness. RESULTS: A total of 56 patients were analyzed in troponin tertiles: nativeT1 and extracellular volume (ECV) values (expressed as means ±â€…standard deviations) increased across tertiles: nativeT1 (1006 ±â€…27 ms vs 1016 ±â€…27 ms vs 1034 ±â€…37 ms, ptrend = 0.006) and ECV (22 ±â€…3% vs 23 ±â€…1.9% vs 25 ±â€…3%, ptrend = 0.007). Cardiac troponin I concentrations correlated with native T1(R = 0.33, P = .012) and ECV (R = 0.3, P = .025), and were independently associated with nativeT1 (P = .049) and ventricular mass index (P = .041) in multivariable analysis. CONCLUSION: In patients with chronic coronary artery disease and structurally normal hearts, troponin I concentrations correlated with T1 mapping parameters, suggesting that diffuse edema or fibrosis scattered in normal myocardium might be associated with chronic troponin release.

Two-Year Follow-Up of Chronic Ischemic Heart Disease Patients in a Specialized Center in Brazil. / Acompanhamento de Dois Anos de Pacientes com Cardiopatia Isquêmica Crônica em um Centro Especializado no Brasil.

The incidence of cardiovascular events in patients with chronic ischemic heart disease (CIHD) may vary significantly among countries. Although populous, Brazil is often underrepresented in international records. This study aimed to describe the quality of care and the two-year incidence of cardiovascular events and associated prognostic factors in CIHD patients in a tertiary public health care center in Brazil. Patients with CIHD who reported for clinical evaluation at Instituto do Coração (São Paulo, Brazil) were registered and followed for two years. The primary endpoint was a composite of myocardial infarction (MI), stroke, or death. A significance level of 0.05 was adopted. From January 2016 to December 2018, 625 participants were included in the study. Baseline characteristics show that 33.1% were women, median age 66.1 [59.6 - 71.9], 48.6% had diabetes, 83.1% had hypertension, 62.6% had previous MI, and 70.4% went through some revascularization procedure. At a median follow-up (FU) of 881 days, we noted 37 (7.05%) primary endpoints. After adjustments, age, previous stroke, and LDL-cholesterol were independently associated with the primary endpoint. Comparing baseline versus FU, participants experienced relief of angina based on the Canadian Cardiovascular Society (CCS) scale according to the following percentages: 65.7% vs. 81.7% were asymptomatic and 4.2% vs. 2.9% CCS 3 or 4 (p < 0.001). They also experienced better quality of medication prescription: 65.8% vs. 73.6% (p < 0.001). However, there was no improvement in LDL-cholesterol or blood pressure control. This study shows that CIHD patients had a two-year incidence of the primary composite endpoint of 7.05%, and the reduction of LDL-cholesterol was the only modifiable risk factor associated with prognosis.

A incidência de eventos cardiovasculares em pacientes com doença cardíaca isquêmica crônica (DCIC) pode variar significativamente entre os países. Embora populoso, o Brasil é frequentemente sub-representado nos registros internacionais. Este estudo teve como objetivo descrever a qualidade do atendimento e a incidência de eventos cardiovasculares em dois anos, além de fatores prognósticos associados em pacientes com DCIC em um centro terciário de saúde pública no Brasil. Pacientes com DCIC que compareceram para avaliação clínica no Instituto do Coração (São Paulo, Brasil) foram cadastrados e acompanhados por dois anos. O desfecho primário foi um composto de infarto do miocárdio (IM), acidente vascular encefálico ou morte. Um nível de significância de 0,05 foi adotado. De janeiro de 2016 a dezembro de 2018, 625 participantes foram incluídos no estudo. As características basais mostram que 33,1% eram mulheres, a idade mediana era de 66,1 [59,6 ­ 71,9], 48,6% tinham diabetes, 83,1% tinham hipertensão, 62,6% tinham IM prévio e 70,4% passaram por algum procedimento de revascularização. Em um acompanhamento mediano de 881 dias, 37 (7,05%) desfechos primários foram observados. Após ajustes, idade, acidente vascular encefálico prévio e colesterol LDL foram independentemente associados ao desfecho primário. Comparando a linha de base com o acompanhamento, os participantes relataram alívio da angina com base na escala da Sociedade Cardiovascular Canadense (SCC) de acordo com as seguintes porcentagens: 65,7% vs. 81,7% eram assintomáticos e 4,2% vs. 2,9% eram SCC 3 ou 4 (p < 0,001). Eles também relataram melhor qualidade na prescrição de medicamentos: 65,8% vs. 73,6% (p < 0,001). No entanto, não houve melhora no colesterol LDL ou no controle da pressão arterial. O presente estudo mostra que pacientes com DCIC apresentaram uma incidência de 7,05% do desfecho primário composto em um período de dois anos, sendo a diminuição do colesterol LDL o único fator de risco modificável associado ao prognóstico.

Hypotheses, rationale, design, and methods for prognostic evaluation of cardiac biomarker elevation after percutaneous and surgical revascularization in the absence of manifest myocardial infarction. A comparative analysis of biomarkers and cardiac magnetic resonance. The MASS-V Trial.

BACKGROUND: Although the release of cardiac biomarkers after percutaneous (PCI) or surgical revascularization (CABG) is common, its prognostic significance is not known. Questions remain about the mechanisms and degree of correlation between the release, the volume of myocardial tissue loss, and the long-term significance. Delayed-enhancement of cardiac magnetic resonance (CMR) consistently quantifies areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac biomarkers, we will evaluate the extent of irreversible injury in patients undergoing PCI and CABG and relate it to postprocedural modifications in cardiac biomarkers and long-term prognosis. METHODS/DESIGN: The study will include 150 patients with multivessel coronary artery disease (CAD) with left ventricle ejection fraction (LVEF) and a formal indication for CABG; 50 patients will undergo CABG with cardiopulmonary bypass (CPB); 50 patients with the same arterial and ventricular condition indicated for myocardial revascularization will undergo CABG without CPB; and another 50 patients with CAD and preserved ventricular function will undergo PCI using stents. All patients will undergo CMR before and after surgery or PCI. We will also evaluate the release of cardiac markers of necrosis immediately before and after each procedure. Primary outcome considered is overall death in a 5-year follow-up. Secondary outcomes are levels of CK-MB isoenzyme and I-Troponin in association with presence of myocardial fibrosis and systolic left ventricle dysfunction assessed by CMR. DISCUSSION: The MASS-V Trial aims to establish reliable values for parameters of enzyme markers of myocardial necrosis in the absence of manifest myocardial infarction after mechanical interventions. The establishments of these indices have diagnostic value and clinical prognosis and therefore require relevant and different therapeutic measures. In daily practice, the inappropriate use of these necrosis markers has led to misdiagnosis and therefore wrong treatment. The appearance of a more sensitive tool such as CMR provides an unprecedented diagnostic accuracy of myocardial damage when correlated with necrosis enzyme markers. We aim to correlate laboratory data with imaging, thereby establishing more refined data on the presence or absence of irreversible myocardial injury after the procedure, either percutaneous or surgical, and this, with or without the use of cardiopulmonary bypass.

Sex Differences in Cardiovascular Disease Mortality in Brazil between 1996 and 2019.

BACKGROUND: cardiovascular diseases (CVD) are Brazil's leading causes of death in women and men. This study analyzed age-adjusted death rate (DRaj) trends from all causes of death (ACD), CVD, ischemic heart disease (IHD), and stroke in women and men aged 35 to 74 years from 1996 to 2019. METHODS: We analyzed DRaj trends for all causes of death (ACD), CVD, IHD, and stroke. Data were from the Ministry of Health mortality database. Joinpoint Regression Program™ performed trend analysis and adjustments in death rates. Average annual percentage change (AAPC) determined the intensity of changes. RESULTS: In women, DRaj reduced for ACD (AAPC = -1.6%); CVD (AAPC = -2.6%); IHD (AAPC = -1.9%); and stroke (AAPC = -4.6%) (p < 0.001 for all). In men, ACD reduced from 1996 to 2004 (AAPC = -0.9%; p < 0.001), from 2012 to 2019 (AAPC = -1.9%; p < 0.001), and unchanged from 2004 to 2012; CVD (AAPC = -2.1%); IHD (AAPC = -1.5%); stroke (AAPC = -4.9%) (p < 0.001 for all) reduced from 1996 to 2019. From 1996 to 2019, the male/female ratio for ACD remained unchanged. CVD increased from 1.58 to 1.83, IHD from 1.99 to 2.30, and stroke from 1.52 to 1.83. CONCLUSION: ACD, CVD, IHD, and stroke were reduced more significantly in women, and the ratio of CVD, IHD, and CVD in men and women increased more in men. Future studies will be needed to determine the main factors responsible for a better outcome in women.

A red wine intervention does not modify plasma trimethylamine N-oxide but is associated with broad shifts in the plasma metabolome and gut microbiota composition.

BACKGROUND: Gut microbiota profiles are closely related to cardiovascular diseases through mechanisms that include the reported deleterious effects of metabolites, such as trimethylamine N-oxide (TMAO), which have been studied as diagnostic and therapeutic targets. Moderate red wine (RW) consumption is reportedly cardioprotective, possibly by affecting the gut microbiota. OBJECTIVES: To investigate the effects of RW consumption on the gut microbiota, plasma TMAO, and the plasma metabolome in men with documented coronary artery disease (CAD) using a multiomics assessment in a crossover trial. METHODS: We conducted a randomized, crossover, controlled trial involving 42 men (average age, 60 y) with documented CAD comparing 3-wk RW consumption (250 mL/d, 5 d/wk) with an equal period of alcohol abstention, both preceded by a 2-wk washout period. The gut microbiota was analyzed via 16S rRNA high-throughput sequencing. Plasma TMAO was evaluated by LC-MS/MS. The plasma metabolome of 20 randomly selected participants was evaluated by ultra-high-performance LC-MS/MS. The effect of RW consumption was assessed by individual comparisons using paired tests during the abstention and RW periods. RESULTS: Plasma TMAO did not differ between RW intervention and alcohol abstention, and TMAO concentrations showed low intraindividual concordance over time, with an intraclass correlation coefficient of 0.049 during the control period. After RW consumption, there was significant remodeling of the gut microbiota, with a difference in ß diversity and predominance of Parasutterella, Ruminococcaceae, several Bacteroides species, and Prevotella. Plasma metabolomic analysis revealed significant changes in metabolites after RW consumption, consistent with improved redox homeostasis. CONCLUSIONS: Modulation of the gut microbiota may contribute to the putative cardiovascular benefits of moderate RW consumption. The low intraindividual concordance of TMAO presents challenges regarding its role as a cardiovascular risk biomarker at the individual level. This study was registered at clinical trials.gov as NCT03232099.

Ten-year follow-up survival of the Medicine, Angioplasty, or Surgery Study (MASS II): a randomized controlled clinical trial of 3 therapeutic strategies for multivessel coronary artery disease.

BACKGROUND: This study compared the 10-year follow-up of percutaneous coronary intervention (PCI), coronary artery surgery (CABG), and medical treatment (MT) in patients with multivessel coronary artery disease, stable angina, and preserved ventricular function. METHODS AND RESULTS: The primary end points were overall mortality, Q-wave myocardial infarction, or refractory angina that required revascularization. All data were analyzed according to the intention-to-treat principle. At a single institution, 611 patients were randomly assigned to CABG (n=203), PCI (n=205), or MT (n=203). The 10-year survival rates were 74.9% with CABG, 75.1% with PCI, and 69% with MT (P=0.089). The 10-year rates of myocardial infarction were 10.3% with CABG, 13.3% with PCI, and 20.7% with MT (P<0.010). The 10-year rates of additional revascularizations were 7.4% with CABG, 41.9% with PCI, and 39.4% with MT (P<0.001). Relative to the composite end point, Cox regression analysis showed a higher incidence of primary events in MT than in CABG (hazard ratio 2.35, 95% confidence interval 1.78 to 3.11) and in PCI than in CABG (hazard ratio 1.85, 95% confidence interval 1.39 to 2.47). Furthermore, 10-year rates of freedom from angina were 64% with CABG, 59% with PCI, and 43% with MT (P<0.001). CONCLUSIONS: Compared with CABG, MT was associated with a significantly higher incidence of subsequent myocardial infarction, a higher rate of additional revascularization, a higher incidence of cardiac death, and consequently a 2.29-fold increased risk of combined events. PCI was associated with an increased need for further revascularization, a higher incidence of myocardial infarction, and a 1.46-fold increased risk of combined events compared with CABG. Additionally, CABG was better than MT at eliminating anginal symptoms. Clinical Trial Registration Information- URL: http://www.controlled-trials.com. REGISTRATION NUMBER: ISRCTN66068876.

Five-year follow-up of a randomized comparison between off-pump and on-pump stable multivessel coronary artery bypass grafting. The MASS III Trial.

BACKGROUND: Coronary artery bypass graft surgery with cardiopulmonary bypass is a safe, routine procedure. Nevertheless, significant morbidity remains, mostly because of the body's response to the nonphysiological nature of cardiopulmonary bypass. Few data are available on the effects of off-pump coronary artery bypass graft surgery (OPCAB) on cardiac events and long-term clinical outcomes. METHODS AND RESULTS: In a single-center randomized trial, 308 patients undergoing coronary artery bypass graft surgery were randomly assigned: 155 to OPCAB and 153 to on-pump CAB (ONCAB). Primary composite end points were death, myocardial infarction, further revascularization (surgery or angioplasty), or stroke. After 5-year follow-up, the primary composite end point was not different between groups (hazard ratio 0.71, 95% CI 0.41 to 1.22; P=0.21). A statistical difference was found between OPCAB and ONCAB groups in the duration of surgery (240±65 versus 300±87.5 minutes; P<0.001), in the length of ICU stay (19.5±17.8 versus 43±17.0 hours; P<0.001), time to extubation (4.6±6.8 versus 9.3±5.7 hours; P<0.001), hospital stay (6±2 versus 9±2 days; P<0.001), higher incidence of atrial fibrillation (35 versus 4% of patients; P<0.001), and blood requirements (31 versus 61% of patients; P<0.001), respectively. The number of grafts per patient was higher in the ONCAB than the OPCAB group (2.97 versus 2.49 grafts/patient; P<0.001). CONCLUSIONS: No difference was found between groups in the primary composite end point at 5-years follow-up. Although OPCAB surgery was related to a lower number of grafts and higher episodes of atrial fibrillation, it had no significant implications related to long-term outcomes. Clinical Trial Registration-URL: http://www.controlled-trials.com. Unique identifier: ISRCTN66068876.

Cardiovascular and Cancer Death Rates in the Brazilian Population Aged 35 to 74 Years, 1996-2017. / Taxas de Mortalidade por Doenças Cardiovasculares e Câncer na População Brasileira com Idade entre 35 e 74 Anos, 1996-2017.

BACKGROUND: Cardiovascular diseases (CVD) and cancer are the main causes of death worldwide. These diseases share many risk factors. Control of traditional risk factors for CVD was associated with lower incidence of cancers. OBJECTIVE: To analyze CVD and cancer mortality rate trends in Brazilian population aged 35-74 years from 1996 to 2017. METHODS: Crude and age-adjusted death rate trends were analyzed for all causes of death, CVD, and cancer. Data were obtained from mortality database of the Ministry of Health. Joinpoint Regression Program performed analysis of trends and adjustments in death rates. The degree of changes was determined by the average annual percent change (AAPC). Level of statistical significance was set at p <0.05. RESULTS: Mortality from all causes of death (AAPC=-1.6%; p<0.001), CVD (AAPC=-2.3; p<0.001), ischemic heart disease (IHD) (AAPC=-1.6; p<0.001) and stroke (AAPC=-3.7; p<0.001) declined. Same trends were observed for CVD (p<0.001) in men and women. Death rates from all causes of cancer (AAPC=-0.1; p=0.201), in men (AAPC=-0.1; p=0.193) and in women (AAPC=-0.1; p=0,871) remained unchanged. In 2002, mortality from cancer exceeded the sum of deaths from IHD and stroke. If trends continue, cancer mortality will also exceed mortality from CVD by 2024. In women, death rates from breast, lung and colon cancer increased, and from cervical and gastric cancers decreased. In men, mortality from lung, stomach and esophagus cancer decreased, and from prostate cancer remained unchanged. CONCLUSION: CVD are currently the leading cause of death in Brazil, but death rates from cancer will exceed those from CVD in a few years.

FUNDAMENTO: As doenças cardiovasculares (DCV) e câncer são as principais causas de morte no mundo. Essas doenças apresentam muitos fatores de risco em comum, e o controle de fatores de risco tradicionais para DCV foi associado com menor incidência de câncer. OBJETIVO: Analisar tendências nas taxas de mortalidade por câncer na população brasileira com idade entre 35 e 74 anos de 1996 a 2017. MÉTODOS: As tendências nas taxas de mortalidade (bruta e ajustada por idade) foram analisadas quanto a todas as causas de morte, DCV e câncer. Os dados foram obtidos do banco de dados de mortalidade do Ministério da Saúde. O programa Joinpoint Regression foi usado para análise das tendências e ajustes nas taxas de saúde. O grau de mudanças nas taxas foi determinado pela variação percentual anual média (VPAM). O nível de significância estatística foi estabelecido em p<0,05. RESULTADOS: A mortalidade por todas as causas (VPAM=-1,6%; p<0,001), CVD (VPAM =-2,3; p<0,001), doenças isquêmicas do coração (DIC) (VPAM =-1,6; p<0,001) e doenças cerebrovasculares (DCbV) (VPAM =-3.7; p<0.001) diminuiu. As mesmas tendências foram observadas para DCV em homens e mulheres (p<0,001). As taxas de mortalidade por todos os tipos de câncer (AAPC=-0,1; p=0,201), em homens (VPAM =-0,1; p=0,193) e mulheres (VPAM =-0,1; p=0,871) permaneceram inalteradas. Em 2002, a mortalidade por câncer excedeu a soma de mortes por DIC e DCbV. Se as tendências continuarem, a mortalidade por câncer também excederá a mortalidade por DCV até 2024. Nas mulheres, a mortalidade por câncer de mama, pulmão e cólon, aumentou, e a mortalidade por câncer de colo de útero e de estômago diminuiu. Nos homens, a mortalidade por câncer de pulmão, estômago, e esôfago diminuiu, e por câncer de próstata permaneceu inalterada. CONCLUSÃO: As DCV são atualmente as principais causas de morte no Brasil, mas as taxas de morte por câncer irão superar as taxas por DCV em poucos anos.

Association Between Stress Testing-Induced Myocardial Ischemia and Clinical Events in Patients With Multivessel Coronary Artery Disease.

IMPORTANCE: The long-term prognostic implications of myocardial ischemia documented during stress testing in patients with multivessel coronary artery disease (CAD) are unclear. OBJECTIVE: To assess whether documented stress testing-induced myocardial ischemia is associated with major adverse cardiovascular events or ventricular function changes in patients with stable multivessel CAD. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study was conducted using data from a single-center randomized clinical trial (Medicine, Angioplasty, or Surgery Study [MASS] II) to examine the association of myocardial ischemia documented during stress testing at baseline with cardiovascular events and ventricular function changes during follow-up. Participants were previously randomized (May 1, 1995, to May 31, 2000) to medical therapy, percutaneous coronary intervention with bare metal stents, or coronary artery bypass grafting. Event-free survival was estimated by the Kaplan-Meier method, and multivariable Cox regression models were calculated to assess the association between ischemia and the primary composite end point. The vital status was determined on February 28, 2011. Data were analyzed from February 1, 2016, to April 1, 2017. MAIN OUTCOMES AND MEASURES: Cardiovascular events (overall mortality, myocardial infarction, and revascularization for refractory angina) were tracked from the time of randomization to the end of the 10-year follow-up (mean [SD] duration, 11.4 [4.3] years). Myocardial ischemia was assessed at baseline and at 1-year intervals by exercise stress testing, and ventricular function (left ventricular ejection fraction) was assessed by echocardiography at baseline and after 10 years. Patients with documented ischemia were compared with those without ischemia regarding the outcomes and changes in ventricular function. RESULTS: Of 611 participants, 535 underwent exercise stress testing at baseline: 270 with documented ischemia and 265 without. Of these 535 patients, 373 (69.7%) were men, and the mean (SD) age for the entire cohort was 59.7 (9.2) years. No association was found between the presence of ischemia at baseline and survival free of combined cardiovascular events (hazard ratio, 1.00; 95% CI, 0.80-1.27; P = .95) after multivariable adjustment that included CAD initial randomized treatments. In addition, among 320 patients who underwent echocardiographic evaluation, the slight decline in left ventricular ejection fraction after 10 years was similar in both groups (median [SD] difference, -4.9% [18.7%] vs -6.6% [20.0%], respectively, for groups with and without ischemia; P = .97). CONCLUSIONS AND RELEVANCE: In this study, regardless of the therapeutic strategy applied, the presence of documented myocardial ischemia did not appear to be associated with an increased occurrence of major adverse cardiovascular events or changes in ventricular function in patients with multivessel CAD during a long-term follow-up.

Ten-Year Follow-Up of Off-Pump and On-Pump Multivessel Coronary Artery Bypass Grafting: MASS III.

It was a randomized trial, and 308 patients undergoing revascularization were randomly assigned: 155 to off-pump coronary artery bypass (OPCAB) and 153 to on-pump coronary artery bypass (ONCAB). End points were freedom from death, myocardial infarction, revascularization, and cerebrovascular accidents. The rates for 10-year, event-free survival for ONCAB versus OPCAB were 69.6% and 64%, (hazard ratio [HR]: 0.88; 95% confidence interval [CI] 0.86-1.02; P = .41), respectively. Adjusted Cox proportional hazard ratio was similar (HR: 0.92; 95% CI 0.61-1.38, P = .68). A difference occurred between the duration of OPCAB and ONCAB, respectively (4.9 ± 1.5 vs 6.6 ± 1.1 h, P < .001). Statistical differences occurred between OPCAB and ONCAB in the length of intensive care unit (ICU) stay (20 ± 2.5 vs 48 ± 10 hours, P < .001), time to extubation (5.5 ± 4.2 vs 10.2 ± 3.5 hours, P < .001), hospital stay (6.7 ± 1.4 vs 9.2 ± 1.3 days, P < .001), higher incidence of atrial fibrillation (AF; 33 vs 5 patients, P < .001), and blood requirements (46 vs 64 patients, P < .001). Grafts per patient was higher in ONCAB (3.15 vs 2.55 grafts, P < .001). No difference existed between the groups in primary composite end points at 10-year follow-up. Although OPCAB surgery was related to a lower number of grafts and higher incidence of AF, it had no effects related to long-term outcomes.

High ratio of triglycerides to HDL-cholesterol predicts extensive coronary disease.

UNLABELLED: An abnormal ratio of triglycerides to HDL-cholesterol (TG/HDL-c) indicates an atherogenic lipid profile and a risk for the development of coronary disease. OBJECTIVE: To investigate the association between lipid levels, specifically TG/HDL-c, and the extent of coronary disease. METHODS: High-risk patients (n=374) submitted for coronary angiography had their lipid variables measured and coronary disease extent scored by the Friesinger index. RESULTS: The subjects consisted of 220 males and 154 females, age 57.2+/-11.1 years, with total cholesterol of 210+/-50.3 mg/dL, triglycerides of 173.8+/-169.8 mg/dL, HDL-cholesterol (HDL-c) of 40.1+/-12.8 mg/dL, LDL-cholesterol (LDL-c) of 137.3+/-46.2 mg/dL, TG/HDL-c of 5.1+/-5.3, and a Friesinger index of 6.6+/-4.7. The relationship between the extent of coronary disease (dichotomized by a Friesenger index of 5 and lipid levels (normal vs. abnormal) was statistically significant for the following: triglycerides, odds ratio of 2.02 (1.31-3.1; p=0.0018); HDL-c, odds ratio of 2.21 (1.42-3.43; p=0.0005); and TG/HDL-c, odds ratio of 2.01(1.30-3.09; p=0.0018). However, the relationship was not significant between extent of coronary disease and total cholesterol [1.25 (0.82-1.91; p=0.33)] or LDL-c [1.47 (0.96-2.25; p=0.0842)]. The chi-square for linear trends for Friesinger >4 and lipid quartiles was statistically significant for triglycerides (p=0.0017), HDL-c (p=0.0001), and TG/HDL-c (p=0.0018), but not for total cholesterol (p=0.393) or LDL-c (p=0.0568). The multivariate analysis by logistic regression OR gave 1.3+/-0.79 (p= .0001) for TG/HDL-c, 0.779+/-0.074 (p= .0001) for HDL-c, and 1.234+/-0.097 (p=0.03) for LDL. Analysis of receiver operating characteristic curves showed that only TG/HDL-c and HDL-c were useful for detecting extensive coronary disease, with the former more strongly associated with disease. CONCLUSIONS: Although some lipid variables were associated with the extent of coronary disease, the ratio of triglycerides to HDL-cholesterol showed the strongest association with extent.

Acompanhamento de Dois Anos de Pacientes com Cardiopatia Isquêmica Crônica em um Centro Especializado no Brasil / Two-Year Follow-Up of Chronic Ischemic Heart Disease Patients in a Specialized Center in Brazil

Resumo Fundamento A incidência de eventos cardiovasculares em pacientes com doença cardíaca isquêmica crônica (DCIC) pode variar significativamente entre os países. Embora populoso, o Brasil é frequentemente sub-representado nos registros internacionais. Objetivos Este estudo teve como objetivo descrever a qualidade do atendimento e a incidência de eventos cardiovasculares em dois anos, além de fatores prognósticos associados em pacientes com DCIC em um centro terciário de saúde pública no Brasil. Métodos Pacientes com DCIC que compareceram para avaliação clínica no Instituto do Coração (São Paulo, Brasil) foram cadastrados e acompanhados por dois anos. O desfecho primário foi um composto de infarto do miocárdio (IM), acidente vascular encefálico ou morte. Um nível de significância de 0,05 foi adotado. Resultados De janeiro de 2016 a dezembro de 2018, 625 participantes foram incluídos no estudo. As características basais mostram que 33,1% eram mulheres, a idade mediana era de 66,1 [59,6 - 71,9], 48,6% tinham diabetes, 83,1% tinham hipertensão, 62,6% tinham IM prévio e 70,4% passaram por algum procedimento de revascularização. Em um acompanhamento mediano de 881 dias, 37 (7,05%) desfechos primários foram observados. Após ajustes, idade, acidente vascular encefálico prévio e colesterol LDL foram independentemente associados ao desfecho primário. Comparando a linha de base com o acompanhamento, os participantes relataram alívio da angina com base na escala da Sociedade Cardiovascular Canadense (SCC) de acordo com as seguintes porcentagens: 65,7% vs. 81,7% eram assintomáticos e 4,2% vs. 2,9% eram SCC 3 ou 4 (p < 0,001). Eles também relataram melhor qualidade na prescrição de medicamentos: 65,8% vs. 73,6% (p < 0,001). No entanto, não houve melhora no colesterol LDL ou no controle da pressão arterial. Conclusão O presente estudo mostra que pacientes com DCIC apresentaram uma incidência de 7,05% do desfecho primário composto em um período de dois anos, sendo a diminuição do colesterol LDL o único fator de risco modificável associado ao prognóstico.

Abstract Background The incidence of cardiovascular events in patients with chronic ischemic heart disease (CIHD) may vary significantly among countries. Although populous, Brazil is often underrepresented in international records. Objectives This study aimed to describe the quality of care and the two-year incidence of cardiovascular events and associated prognostic factors in CIHD patients in a tertiary public health care center in Brazil. Methods Patients with CIHD who reported for clinical evaluation at Instituto do Coração (São Paulo, Brazil) were registered and followed for two years. The primary endpoint was a composite of myocardial infarction (MI), stroke, or death. A significance level of 0.05 was adopted. Results From January 2016 to December 2018, 625 participants were included in the study. Baseline characteristics show that 33.1% were women, median age 66.1 [59.6 - 71.9], 48.6% had diabetes, 83.1% had hypertension, 62.6% had previous MI, and 70.4% went through some revascularization procedure. At a median follow-up (FU) of 881 days, we noted 37 (7.05%) primary endpoints. After adjustments, age, previous stroke, and LDL-cholesterol were independently associated with the primary endpoint. Comparing baseline versus FU, participants experienced relief of angina based on the Canadian Cardiovascular Society (CCS) scale according to the following percentages: 65.7% vs. 81.7% were asymptomatic and 4.2% vs. 2.9% CCS 3 or 4 (p < 0.001). They also experienced better quality of medication prescription: 65.8% vs. 73.6% (p < 0.001). However, there was no improvement in LDL-cholesterol or blood pressure control. Conclusion This study shows that CIHD patients had a two-year incidence of the primary composite endpoint of 7.05%, and the reduction of LDL-cholesterol was the only modifiable risk factor associated with prognosis.

Accumulation of chylomicron remnants and impaired vascular reactivity occur in subjects with isolated low HDL cholesterol: effects of niacin treatment.

Fasting hypertriglyceridemia relates with high-density lipoprotein (HDL) cholesterol, but it is not known whether low HDL cholesterol is associated with disturbances of chylomicron metabolism. To clarify this issue this metabolism was studied in subjects with low HDL cholesterol together with vascular reactivity and evaluation of no-flush niacin treatment. Thirty men with HDL < 1.04 mmol/L and no other risk factors for coronary artery disease (CAD) and 11 normal controls with HDL > 1.04 mmol/L were studied. The plasma kinetics of a chylomicron-like emulsion labeled with 14C-cholesterol oleate (CO) and 3H-triolein (TG) was determined and the fractional clearance rate (FCR, min(-1)) was calculated. Vascular reactivity was evaluated using high-resolution ultrasonography. CO FCR was markedly reduced in the low HDL group compared to controls (3.6 x 10(-3) +/- 5.1 x 10(-3) min(-1) versus 12.2 x 10(-3) +/- 8.4 x 10(-3) min(-1), p < 0.001) but TG FCR was similar. Flow-mediated dilation (FMD) was diminished in low HDL (7.4 +/- 4.1 versus 12.8 +/- 4.6%, p < 0.001), whereas nitrate-mediated dilation was similar. Twenty-two low HDL subjects with reduced FMD were randomized into two groups, one given 1.5 g/day niacin and a placebo group. After 3-month treatment, plasma lipids and chylomicron kinetics were not changed by niacin treatment but FMD improved to normal values (5.44 +/- 1.89 to 11.13 +/- 3.4%, p < 0.01). In conclusion, isolated low HDL cholesterol subjects may also bear chylomicron remnant accumulation and endothelial dysfunction, which highlight the importance of their preventive treatment.