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Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 105 mL·min –1 ·1.73 m –2 , compared with those with eGFR between 60 and 105 mL·min –1 ·1.73 m –2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR –1 ·1.73 m –2 , with a 14% (95% CI, 3%–27%) higher CHD risk per 5 mL·min –1 ·1.73 m –2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min –1 ·1.73 m –2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Background: ST-segment elevation acute myocardial infarction (STEMI) is a pathological process that involves cardiac muscle tissue death. Intravenous thrombolysis with fibrinolytics or primary percutaneous coronary intervention (PCI), an invasive technique, can be performed for tissue revascularization. PCI has been preferred as compared to non-invasive methods, although few studies have described its use in Brazil. Objectives: The aim of the present study was to analyze data on the use of primary PCI and investigate the relevance of hospitalizations for the treatment of STEMI in the country. Methods: A descriptive, cross-sectional analysis of data from the Brazilian Unified Health system (SUS) Department of Informatics (DATASUS) from 2010 to 2019 was conducted. Results: Hospitalizations for STEMI represented 0.6% of all hospital admissions in Brazil in the analyzed period, 0.9% of hospital costs, and 2.1% of deaths. The number of hospitalizations due to STEMI was 659,811, and 82,793 for PCIs. Length of hospital stay was 36.0% shorter and mortality rate was 53.3% lower in PCI. The mean cost of PCI was 3.5-fold higher than for treatment of STEMI. Conclusions: Data on hospitalizations for STEMI treatment in Brazil revealed high hospitalization and mortality rates, elevated costs, and long hospital stay. Although primary PCI is a more expensive and less used technique than other methods, it can reduce the length of hospital stay and mortality in the treatment of STEMI.

Cardiovascular mortality increases with decreasing renal function although the cause is yet unknown. Here, we have investigated whether low chronic inflammation in chronic kidney diseases (CKD) could contribute to increased risk for coronary artery diseases (CAD). Thus, a prospective case&ndash, control study was conducted in patients with CAD and CKD undergoing coronary artery bypass graft surgery with the aim of detecting differences in cardiovascular outcomes, epicardial adipose tissue volume, and inflammatory marker activity associated with renal dysfunction. Expression of membrane CD14 and CD16, inflammatory cytokines and chemokines, mitogen-activated protein (MAP) kinases and hsa-miR-30a-5p were analyzed in peripheral blood mononuclear cells (PBMCs). Epicardial fat volume and tissue inflammation in perivascular adipose tissue and in the aorta were also studied. In the present study, 151 patients were included, 110 with CAD (51 with CKD) and 41 nonCAD controls (15 with CKD). CKD increased the risk of cardiac surgery&ndash, associated acute kidney injury (CSA-AKI) as well as the 30-day mortality after cardiac surgery. Higher counts of CD14++CD16+ monocytes were associated with vascular inflammation, with an increased expression of IL1&beta, and with CKD in CAD patients. Expression of hsa-miR-30a-5p was correlated with hypertension. We conclude that CKD patients show an increased risk of CSA-AKI and mortality after cardiovascular surgery, associated with the expansion of the CD14++CD16+ subset of proinflammatory monocytes and with IL1&beta, expression. We propose that inflammation associated with CKD may contribute to atherosclerosis (ATH) pathogenesis.

Atherosclerosis (ATH) and coronary artery disease (CAD) are chronic inflammatory diseases with an important genetic background; they derive from the cumulative effect of multiple common risk alleles, most of which are located in genomic noncoding regions. These complex diseases behave as nonlinear dynamical systems that show a high dependence on their initial conditions; thus, long-term predictions of disease progression are unreliable. One likely possibility is that the nonlinear nature of ATH could be dependent on nonlinear correlations in the structure of the human genome. In this review, we show how chaos theory analysis has highlighted genomic regions that have shared specific structural constraints, which could have a role in ATH progression. These regions were shown to be enriched with repetitive sequences of the Alu family, genomic parasites that have colonized the human genome, which show a particular secondary structure and are involved in the regulation of gene expression. Here, we show the impact of Alu elements on the mechanisms that regulate gene expression, especially highlighting the molecular mechanisms via which the Alu elements alter the inflammatory response. We devote special attention to their relationship with the long noncoding RNA (lncRNA); antisense noncoding RNA in the INK4 locus (ANRIL), a risk factor for ATH; their role as microRNA (miRNA) sponges; and their ability to interfere with the regulatory circuitry of the (nuclear factor kappa B) NF-κB response. We aim to characterize ATH as a nonlinear dynamic system, in which small initial alterations in the expression of a number of repetitive elements are somehow amplified to reach phenotypic significance.

INTRODUCTION Postprandial lipemia (PPL) influences the development of atherosclerosis. However, there are still significant gaps to fully understanding of postprandial metabolism and its regulating factors. OBJECTIVES Main objective: To determine whether metabolic syndrome (MetS) traits influence the PPL of coronary patients, and whether this influence depends on the number of MetS criteria. Secondary objectives: 1) To investigate whether the number of criteria of metabolic syndrome may predict the degree of postprandial response in patients with normal fasting triglycerides (TGs); 2) To determine the exact contribution of the presence of MetS to age-associated enlarged PPL; 3) To explore the phenotypic flexibility of high risk patients, measured with an oral fat tolerance test (OFTT), according to different cardio-metabolic abnormalities and body mass index (BMI). METHODS We developed two independent studies: A first one where we compared the PPL response to a rich fatty meal of 88 healthy young men ( 40; and 20 healthy people > 65) (all ApoE3/E3), at fasting state and at 2nd and 4th postprandial hours; and a second one where 1002 coronary artery disease patients from the CORDIOPREV study were submitted at the beginning of the study to an OFTT with 0.7 g fat/kg body weight and serial blood test analyzing lipid fractions were drawn at 0, 1, 2, 3 and 4 hours during the postprandial state. Patients were classified according to the presence of MetS and the number of its traits. We also explored in that cohort the dynamic response according to six body size phenotypes: (i) normal weight, metabolically healthy; (ii) normal weight, metabolically abnormal; (iii) overweight, metabolically healthy; (iv) overweight, metabolically abnormal; (v) obese, metabolically healthy; and (vi) obese, metabolically abnormal. RESULTS In the first study, we didn’t find differences between the healthy young men and the healthy elderly. MetS patients displayed a higher postprandial TG area below the curve than the other two cohorts p < 0.001. In the CORDIOPREV study, PPL response was directly related to the presence of MetS. We found a positive association between the number of MetS criteria and the response of postprandial plasma TGs (p= 0.001), area under the curve (AUC) of TGs (p= 0.001) and incremental AUC of TGs (p= 0.001). However, the influence of them on postprandial TGs remained statistically significant only in those patients without basal hypertriglyceridemia. Only fasting TGs, fasting glucose and waist circumference appeared as significant independent contributors (p < 0.05). Metabolically healthy patients displayed lower PPL compared with those metabolically abnormal, independently whether or not they were obese (p < 0.001 and p < 0.01, respectively). CONCLUSIONS MetS may account for the differences in PPL that have been attributed to age. Fasting TGs are the major contributors to the postprandial TGs levels. MetS influences the PPL in patients with coronary heart disease, particularly in non-hypertriglyceridemic patients. Finally, our findings showed that certain types of the metabolic phenotypes of obesity are more favorable modulating their response to a fat load test. To identify these phenotypes may be the best strategy for personalized treatment of obesity. INTRODUCCIÓN La lipemia postprandial (LPP) influye en el desarrollo de arteriosclerosis. Sin embargo, existen importantes áreas de incertidumbre para comprender completamente el metabolismo energético postprandial y sus factores reguladores. OBJETIVOS Objetivo principal: Determinar si los rasgos de síndrome metabólico (SMet) influyen en la LPP en pacientes coronarios, y si esta influencia depende del número de criterios presentes de SMet. Objetivos secundarios: 1) investigar si el número de criterios de SMet puede predecir el grado de respuesta postprandial en pacientes con triglicéridos (TGs) plasmáticos en ayunas normales; 2) determinar la contribución exacta de la presencia de SMet en la respuesta anormal de LPP asociada a la edad; y 3) explorar la flexibilidad fenotípica de pacientes de alto riesgo, medida a través de un test de sobrecarga oral de grasa (TSOG), de acuerdo a diferentes anormalidades cardiometabólicas y al índice de masa corporal (IMC). MÉTODOS Se han desarrollado dos estudios independientes: un primer estudio comparando la respuesta en la LPP a una comida rica en grasa en 88 hombres jóvenes sanos (40 años, y 20 sanos >65 años) (todos ApoE3/E3), en ayunas y a las 2 y 4 horas tras la sobrecarga; y un segundo estudio donde 1002 pacientes con enfermedad coronaria pertenecientes al estudio CORDIOPREV completaron al inicio del mismo un TSOG con 0.7 g de grasa/kg, con extracciones sanguíneas a las 0, 1, 2, 3 y 4 horas durante el estado postprandial. Los pacientes fueron clasificados según la presencia de SMet y el número de sus criterios. También se exploró en esta cohorte de pacientes coronarios su respuesta dinámica de acuerdo a seis fenotipos diferentes corporales: (i) normopeso, metabólicamente sano; (ii) normopeso, metabólicamente enfermo; (iii) sobrepeso, metabólicamente sano; (iv) sobrepeso, metabólicamente enfermo; (v) obeso, metabólicamente sano; y (vi) obeso, metabólicamente enfermo. RESULTADOS En nuestro primer estudio, no encontramos diferencias entre los varones sanos jóvenes y los mayores sanos. Los pacientes con SMet mostraron mayor magnitud en la respuesta de TGs postprandiales que los otros dos grupos (p < 0.001). En el estudio CORDIOPREV, la magnitud en la respuesta de la LPP se relacionó directamente con la presencia de SMet. Encontramos una asociación positiva entre el número de criterios de SMet y la respuesta de TGs plasmáticos postprandiales (p= 0.0001), ABC de TGs (p= 0.0001) y el incremento del area bajo la curva (AUC) de TGs plasmáticos (p= 0.001). La influencia de estos criterios sobre los TGs postprandiales sólo se mantuvo significativa en aquellos pacientes sin hipertrigliceridemia basal. Tan sólo la cifras de TGs y glucosa en ayunas, así como el perímetro de cintura se mantuvieron como predictores independientes significativos de LPP (p < 0.05). Los pacientes metabólicamente sanos mostraron menor LPP comparados con aquellos metabólicamente enfermos, independientemente de si eran obesos o no (p< 0.001). CONCLUSIONES La presencia de SMet puede modular las diferencias en LPP que han sido atribuidas a la edad. Las cifras de TG en ayunas son el factor que más influye en el grado de respuesta de TGs plasmáticos postprandiales. El SMet influye en la magnitud de la LPP de pacientes coronarios, especialmente en aquellos sin hipertrigliceridemia basal. Finalmente, nuestros hallazgos muestran que ciertos fenotipos metabólicos de obesidad son más favorables modulando su respuesta a un TSOG. Identificar estos fenotipos podría constituir la mejor estrategia para un tratamiento personalizado de la obesidad.

INTRODUCTION Postprandial lipemia (PPL) influences the development of atherosclerosis. However, there are still significant gaps to fully understanding of postprandial metabolism and its regulating factors. OBJECTIVES Main objective: To determine whether metabolic syndrome (MetS) traits influence the PPL of coronary patients, and whether this influence depends on the number of MetS criteria. Secondary objectives: 1) To investigate whether the number of criteria of metabolic syndrome may predict the degree of postprandial response in patients with normal fasting triglycerides (TGs); 2) To determine the exact contribution of the presence of MetS to age-associated enlarged PPL; 3) To explore the phenotypic flexibility of high risk patients, measured with an oral fat tolerance test (OFTT), according to different cardio-metabolic abnormalities and body mass index (BMI). METHODS We developed two independent studies: A first one where we compared the PPL response to a rich fatty meal of 88 healthy young men ( 40; and 20 healthy people > 65) (all ApoE3/E3), at fasting state and at 2nd and 4th postprandial hours; and a second one where 1002 coronary artery disease patients from the CORDIOPREV study were submitted at the beginning of the study to an OFTT with 0.7 g fat/kg body weight and serial blood test analyzing lipid fractions were drawn at 0, 1, 2, 3 and 4 hours during the postprandial state. Patients were classified according to the presence of MetS and the number of its traits. We also explored in that cohort the dynamic response according to six body size phenotypes: (i) normal weight, metabolically healthy; (ii) normal weight, metabolically abnormal; (iii) overweight, metabolically healthy; (iv) overweight, metabolically abnormal; (v) obese, metabolically healthy; and (vi) obese, metabolically abnormal. RESULTS In the first study, we didn’t find differences between the healthy young men and the healthy elderly. MetS patients displayed a higher postprandial TG area below the curve than the other two cohorts p < 0.001. In the CORDIOPREV study, PPL response was directly related to the presence of MetS. We found a positive association between the number of MetS criteria and the response of postprandial plasma TGs (p= 0.001), area under the curve (AUC) of TGs (p= 0.001) and incremental AUC of TGs (p= 0.001). However, the influence of them on postprandial TGs remained statistically significant only in those patients without basal hypertriglyceridemia. Only fasting TGs, fasting glucose and waist circumference appeared as significant independent contributors (p < 0.05). Metabolically healthy patients displayed lower PPL compared with those metabolically abnormal, independently whether or not they were obese (p < 0.001 and p < 0.01, respectively). CONCLUSIONS MetS may account for the differences in PPL that have been attributed to age. Fasting TGs are the major contributors to the postprandial TGs levels. MetS influences the PPL in patients with coronary heart disease, particularly in non-hypertriglyceridemic patients. Finally, our findings showed that certain types of the metabolic phenotypes of obesity are more favorable modulating their response to a fat load test. To identify these phenotypes may be the best strategy for personalized treatment of obesity. INTRODUCCIÓN La lipemia postprandial (LPP) influye en el desarrollo de arteriosclerosis. Sin embargo, existen importantes áreas de incertidumbre para comprender completamente el metabolismo energético postprandial y sus factores reguladores. OBJETIVOS Objetivo principal: Determinar si los rasgos de síndrome metabólico (SMet) influyen en la LPP en pacientes coronarios, y si esta influencia depende del número de criterios presentes de SMet. Objetivos secundarios: 1) investigar si el número de criterios de SMet puede predecir el grado de respuesta postprandial en pacientes con triglicéridos (TGs) plasmáticos en ayunas normales; 2) determinar la contribución exacta de la presencia de SMet en la respuesta anormal de LPP asociada a la edad; y 3) explorar la flexibilidad fenotípica de pacientes de alto riesgo, medida a través de un test de sobrecarga oral de grasa (TSOG), de acuerdo a diferentes anormalidades cardiometabólicas y al índice de masa corporal (IMC). MÉTODOS Se han desarrollado dos estudios independientes: un primer estudio comparando la respuesta en la LPP a una comida rica en grasa en 88 hombres jóvenes sanos (40 años, y 20 sanos >65 años) (todos ApoE3/E3), en ayunas y a las 2 y 4 horas tras la sobrecarga; y un segundo estudio donde 1002 pacientes con enfermedad coronaria pertenecientes al estudio CORDIOPREV completaron al inicio del mismo un TSOG con 0.7 g de grasa/kg, con extracciones sanguíneas a las 0, 1, 2, 3 y 4 horas durante el estado postprandial. Los pacientes fueron clasificados según la presencia de SMet y el número de sus criterios. También se exploró en esta cohorte de pacientes coronarios su respuesta dinámica de acuerdo a seis fenotipos diferentes corporales: (i) normopeso, metabólicamente sano; (ii) normopeso, metabólicamente enfermo; (iii) sobrepeso, metabólicamente sano; (iv) sobrepeso, metabólicamente enfermo; (v) obeso, metabólicamente sano; y (vi) obeso, metabólicamente enfermo. RESULTADOS En nuestro primer estudio, no encontramos diferencias entre los varones sanos jóvenes y los mayores sanos. Los pacientes con SMet mostraron mayor magnitud en la respuesta de TGs postprandiales que los otros dos grupos (p < 0.001). En el estudio CORDIOPREV, la magnitud en la respuesta de la LPP se relacionó directamente con la presencia de SMet. Encontramos una asociación positiva entre el número de criterios de SMet y la respuesta de TGs plasmáticos postprandiales (p= 0.0001), ABC de TGs (p= 0.0001) y el incremento del area bajo la curva (AUC) de TGs plasmáticos (p= 0.001). La influencia de estos criterios sobre los TGs postprandiales sólo se mantuvo significativa en aquellos pacientes sin hipertrigliceridemia basal. Tan sólo la cifras de TGs y glucosa en ayunas, así como el perímetro de cintura se mantuvieron como predictores independientes significativos de LPP (p < 0.05). Los pacientes metabólicamente sanos mostraron menor LPP comparados con aquellos metabólicamente enfermos, independientemente de si eran obesos o no (p< 0.001). CONCLUSIONES La presencia de SMet puede modular las diferencias en LPP que han sido atribuidas a la edad. Las cifras de TG en ayunas son el factor que más influye en el grado de respuesta de TGs plasmáticos postprandiales. El SMet influye en la magnitud de la LPP de pacientes coronarios, especialmente en aquellos sin hipertrigliceridemia basal. Finalmente, nuestros hallazgos muestran que ciertos fenotipos metabólicos de obesidad son más favorables modulando su respuesta a un TSOG. Identificar estos fenotipos podría constituir la mejor estrategia para un tratamiento personalizado de la obesidad.

Epidemiologic studies show a strong relationship between blood pressure (BP) measurements and the incidence of major cardiovascular events [(1)][1]. The primary basis for the treatment of hypertension has been the belief that reducing BP provides cardiovascular protection. This is supported by

Background and Purpose: Selecting an ideal antithrombotic therapy for elderly patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) can be challenging since they have a higher thromboembolic and bleeding risk than younger patients. The current study aimed to assess the efficacy and safety of triple therapy (TT: oral anticoagulation plus dual antiplate- let therapy: aspirin plus clopidogrel) in patients > 75 years of age with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). Methods: A prospective multicenter study was conducted from 2003 to 2012 at 6 Spanish teaching hospitals. A cohort study of consecutive patients with AF undergoing PCI and treated with TT or dual antiplatelet therapy (DAPT) was analyzed. All outcomes were evaluated at 1- year of follow-up. Results: Five hundred and eighty-five patients, 289 (49%) of whom were > 75 years of age (79.6 ± 3.4 years; 33% women) were identified. TT was prescribed in 55.9% of patients at discharge who had a higher thromboembolic risk (CHA 2 DS 2 VASc score: 4.23 ± 1.51 vs 3.76 ± 1.40, p = 0.007 and a higher bleeding risk (HAS-BLED > 3: 88.6% vs 79.2%, p = 0.02) than those on DAPT. Therefore, patients on TT had a lower rate of thromboembolism than those on DAPT (0.6% vs 6.9%, p = 0.004; HR 0.08, 95% CI: 0.01 - 0.70, p = 0.004). Major bleeding events occurred more frequently in patients on TT than in those on DAPT (11.7% vs 2.4%, p = 0.002; HR 5.2, 95% CI: 1.53 - 17.57, p = 0.008). The overall mortality rate was similar in both treatment groups (11.9% vs 13.9%, p = 0.38); however, after adjustment for confounding variables, TT was associated with a reduced mortality rate (HR 0.33, 95% CI: 0.12 - 0.86, p = 0.02). Conclusions In elderly patients with AF undergoing PCI, the use of TT compared to DAPT was associ- ated with reduced thromboembolism and mortality rates, although a higher rate of major bleeding.

BACKGROUND: Epidemiologic studies have suggested that flavonoid intake plays a critical role in the prevention of coronary heart disease. Because atherosclerosis is considered a low-grade inflammatory disease, some feeding trials have analyzed the effects of cocoa (an important source of flavonoids) on inflammatory biomarkers, but the results have been controversial. OBJECTIVE: The objective was to evaluate the effects of chronic cocoa consumption on cellular and serum biomarkers related to atherosclerosis in high-risk patients. DESIGN: Forty-two high-risk volunteers (19 men and 23 women; mean +/- SD age: 69.7 +/- 11.5 y) were included in a randomized crossover feeding trial. All subjects received 40 g cocoa powder with 500 mL skim milk/d (C+M) or only 500 mL skim milk/d (M) for 4 wk. Before and after each intervention period, cellular and serum inflammatory biomarkers related to atherosclerosis were evaluated. RESULTS: Adherence to the dietary protocol was excellent. No significant changes in the expression of adhesion molecules on T lymphocyte surfaces were found between the C+M and M groups. However, in monocytes, the expression of VLA-4, CD40, and CD36 was significantly lower (P = 0.005, 0.028, and 0.001, respectively) after C+M intake than after M intake. In addition, serum concentrations of the soluble endothelium-derived adhesion molecules P-selectin and intercellular adhesion molecule-1 were significantly lower (both P = 0.007) after C+M intake than after M intake. CONCLUSIONS: These results suggest that the intake of cocoa polyphenols may modulate inflammatory mediators in patients at high risk of cardiovascular disease. These antiinflammatory effects may contribute to the overall benefits of cocoa consumption against atherosclerosis. This trial was registered in the Current Controlled Trials at London, International Standard Randomized Controlled Trial Number, at controlled-trials.com as ISRCTN75176807.

SummaryThe progress of retinal imaging techniques has made retinal microvascular circulation easier to study. A number of observational studies were conducted to characterise the different abnormalities encountered and to determine the factors contributing to their onset. Three lesion groups were highlighted, including reduced arteriolar diameter, venular dilatation and retinopathy lesions. Retinal arteriolar narrowing signals the presence of hypertension (current or old) and the risk of hypertension onset. A genetic factor was implicated in this relationship. Venular dilatation and retinopathy correlate with the presence of diabetes, obesity and metabolic disorders. This association appears to be mediated partly by the presence of endothelial dysfunction and inflammation. The relationship between these abnormalities and cardiovascular risk was also studied in a number of longitudinal studies: the presence of retinal microvascular abnormalities is related with an increased risk of cardiovascular morbidity and mortality predominantly in individuals under the age of 75. More specifically, retinopathy is correlated with the presence of cerebral white matter lesions detected by MRI, an increased stroke risk and deterioration in cognitive function. On the cardiovascular level, a correlation was demonstrated between diminished coronary reserve, increased coronary calcifications observed by CT scan, coronary morbidity and mortality, and risk of heart failure. New techniques of retinal imaging, such as laser Doppler flowmetry, are still undergoing assessment and will help further to clarify these correlations.

Background: Retrospective studies based on clinical data and without spirometric confirmation suggest a poorer prognosis of patients with ischemic heart disease (IHD) and chronic obstructive pulmonary disease (COPD) following percutaneous coronary intervention (PCI). The impact of undiagnosed COPD in these patients is unknown. We aimed to evaluate the prognostic impact of COPD – previously or newly diagnosed – in patients with IHD treated with PCI. Methods: Patients with IHD confirmed by PCI were consecutively included. After PCI they underwent forced spirometry and evaluation for cardiovascular risk factors. All-cause mortality, new cardiovascular events, and their combined endpoint were analyzed. Results: A total of 133 patients (78%) male, with a mean (SD) age of 63 (10.12) years were included. Of these, 33 (24.8%) met the spirometric criteria for COPD, of whom 81.8% were undiagnosed. IHD patients with COPD were older, had more coronary vessels affected, and a greater history of previous myocardial infarction. Median follow-up was 934 days (interquartile range [25%–75%]: 546–1,160). COPD patients had greater mortality (P=0.008; hazard ratio [HR]: 8.85; 95% confidence interval [CI]: 1.76–44.47) and number of cardiovascular events (P=0.024; HR: 1.87; 95% CI: 1.04–3.33), even those without a previous diagnosis of COPD (P=0.01; HR: 1.78; 95% CI: 1.12–2.83). These differences remained after adjustment for sex, age, number of coronary vessels affected, and previous myocardial infarction (P=0.025; HR: 1.83; 95% CI: 1.08–3.1), The CATEPOC study was supported in part by Menarini Spain

BACKGROUND: To evaluate the predictive value of carotid atherosclerotic disease (CAD) and intima-media thickness (IMT) on incident cardiovascular disease and mortality in hemodialysis patients. METHODS: Multicenter, observational, prospective study including 110 patients, followed-up to 6 years. Carotid doppler ultrasonographic findings were classified in 4 degrees of severity: 1) IMT 0.9 mm, 3) carotid plaque with stenosis 50%. The associations between IMT and CAD and cardiovascular events, total and cardiovascular mortality were assessed. RESULTS: 83% of the patients had atherosclerotic plaques (CAD degrees 3-4). During follow-up, 29.1% of patients experienced cardiovascular events, and 28.2% died, 38.7% of cardiovascular origin. The presence of plaques was associated with cardiovascular events (p = 0.03) while calcified plaques were associated with both cardiovascular events (p = 0.01), cardiovascular mortality (p = 0.03) and non-significantly with overall mortality (p = 0.08) in the survival analysis. Carotid IMT was not associated with outcomes. Cardiovascular events correlated with CAD severity (HR 2.27, 95% CI 1.13-4.54), age (HR 1.04, 1.01-1.06), previous cardiovascular disease (HR 1.75, 1.05-4.42), dyslipidemia (HR 2.25, 1.11-4.53), lipoprotein (a) (HR 1.01, 1.00-1.02), troponin I (HR 3.89, 1.07-14.18), fibrinogen levels (HR 1.38, 0.98-1.94) and antiplatelet therapy (HR 2.14, 1.04-4.4). In an age-adjusted multivariate model, cardiovascular events were independently associated with previous coronary artery disease (HR 3.29, 1.52-7.15) and lipoprotein (a) (HR 1.01, 1.00-1.02)./nCONCLUSIONS: The presence of carotid plaques and, especially, calcified plaques, are predictors of new cardiovascular events and cardiovascular mortality in hemodialysis patients, while IMT was not. The prognostic value of calcified plaques should be confirmed in future studies. This study was supported in part by the FISS project 03/0791 (a public grant from the Spanish Ministry of Health) ["Fondo de Investigación Sanitaria Instituto Carlos III, Ministerio de Sanidad y Consumo. FIS project 03/0791, http://www.isciii.es/ISCIII/es/contenidos/fd-investigacion/fd-financiacion/convocatorias-ayudas-accion-estrategica-salud.shtml].

An interesting aspect of infection with several infectious agents is the possible association with some diseases apparently not associated with infections. One of the most exciting examples of this is the association of cardiovascular diseases with infection involving several different infectious agents. Cytomegalovirus (CMV) is one of the chief candidates that have been studied. Several epidemiologic reports indicate a possible association of various forms of vascular disease with the presence and titer of viral antibodies. Other studies show the presence of virus, viral antigens or nucleic acid in atherosclerotic lesions. Studies in animal models and cell-culture studies present attractive mechanisms by which the virus may play a role in the etiology of these diseases. However, negative results have also been reported, and more research is needed before the final verdict on this exciting question is presented.

Het Peilstationsproject Hart- en Vaatziekten is uitgevoerd van 1987-1991. In deze periode zijn ruim 36.000 mannen en vrouwen in de leeftijd van 20-59 jaar onderzocht op risicofactoren voor hart- en vaatziekten. Prevalentie van hypercholesterolemie was 16% voor mannen en 13% voor vrouwen, 21% van de mannen en 6% van de vrouwen had een verlaagd HDL-cholesterolgehalte. Acht procent van de mannen en 6% van de vrouwen had hypertensie en 7% van de mannen en 9% van de vrouwen had overgewicht. Veertig procent van de mannen en vrouwen rookte sigaretten, 10% van de mannen en 3% van de vrouwen waren zware drinkers. Ongeveer 1/3 deel van alle mannen en vrouwen was lichamelijk inactief. De prevalentie van hypercholesterolemie daalde over de studieperiode met 3% bij mannen en 2% bij vrouwen, de prevalentie van een verlaagd HDL-cholesterolgehalte nam toe met 9% bij mannen en 1% bij vrouwen. De prevalentie van hypertensie veranderde niet, maar de medicamenteuze behandeling van hypertensie daalde. De prevalentie van overgewicht en lichamelijke inactiviteit steeg wanneer werd gecorrigeerd voor veranderingen in opleidingsniveau over de studieperiode. Het percentage sigaretten rokers daalde met 3% bij mannen en 4% bij vrouwen, het percentage zware drinkers nam af met 3% bij mannen en vrouwen.

PART 1. EFECTE DE LA HIPÒXIA I FACTORS POINFLAMATORIS SOBRE EL REMODELAT CARDÍAC EN CARDIOMIÒCITS VENTRICULARS HUMANS. INTRODUCCIÓ. Els mecanismes moleculars pels quals la isquèmia miocardíaca es tradueix en remodelat ventricular i insuficiència cardíaca són poc coneguts. HIPÒTESI. La hipòxia i factors proinflamatoris són inductors específics de recanvi de matriu extracel•lular en els cardiomiòcits humans. MÈTODES. Cardiomiòcits ventriculars humans adults (cèl•lules AC16) van ser incubats en condicions de tensió reduïda d’oxigen, CoCl2 (activador del factor de transcripció induïble per hipòxia 1, HIF-1), rotenona (inhibidor de HIF-1), TNFα, IL1β, LPS o vehicle durant intervals de temps variables. Un cop completats els períodes d’incubació, van obtenir-se els sobrenadants i el RNA cel•lulars per determinar la secreció cel•lular i l’expressió gènica de factors relacionats amb el recanvi de matriu extracel•lular. RESULTATS. La hipòxia indueix la producció de PIIINP (propèptid aminoterminal del del procolàgen tipus III) i inhibeix la síntesi i producció de TIMP1 (inhibidor tissular de metaloproteinases tipus 1) en els cardiomiòcits. La IL1β estimula la producció de PIIINP, TIMP1 i àcid hialurònic en cardiomiòcits. CONCLUSIÓ. La hipòxia i la IL1β activen el remodelat de matriu extracel•lular en cardiomiòcits ventriculars humans. Els resultats suggereixen que la hipòxia i la IL1-β són factors contribuents a la dilatació ventricular i insuficiència cardíaca en la malaltia cardíaca isquèmica. PART 2. EFECTE DE LA HIPÒXIA SOBRE LA SECRECIÓ DEL PÈPTID NATRIURÈTIC TIPUS B (BNP) EN CARDIOMIÒCITS VENTRICULARS HUMANS. INTRODUCCIÓ. El principal estímul per la síntesi i secreció de BNP es la distensió de la paret cardíaca. Evidències recents suggereixen que la isquèmia cardíaca pot induir també la producció de BNP. HIPÒTESI. La tensió reduïda d’oxigen estimula directament l’expressió gènica i la secreció de BNP en cardiomiòcits ventriculars humans en absència d’estímuls hemodinàmics o neurohormonals. MÈTODES. Cardiomiòcits ventriculars adults (cèl•lules AC16) van ser incubats en condiciones normòxiques o hipòxiques amb o sense la presència de rotenona. L’acumulació de BNP, ANP i VEGF es va mesurar en els sobrenadants cel•lulars. L’expressió gènica d’aquests factors va determinar-se mitjançant PCR a temps real. L’activitat transcripcional de HIF-1 va determinar-se en extractes nuclears cel•lulars mitjançant un enziminmunoassaig lligat a la seqüència d’unió de HIF-1 al DNA. RESULTATS. L’activitat transcripcional de HIF-1 va induir-se en condicions hipòxiques. La hipòxia va estimular la secreció i l’expressió gènica de BNP i VEGF però no d’ANP en els cardiomiòcits. La inhibició de HIF-1 en condicions hipòxiques va disminuir la secreció de BNP i VEGF. CONCLUSIONS. La hipòxia indueix la síntesi i secreció de BNP en cardiomiòcits ventriculars humans a través d’un mecanisme depenent de l’activació transcripcional de HIF-1. PART 3. ESTUDI DE LA SIGNIFICACIÓ CLÍNICA DE LES CONCENTRACIONS PLASMÀTIQUES DE BNP A L’INGRÉS EN PACIENTS AMB SÍNDROME CORONÀRIA AGUDA (SCA). INTRODUCCIÓ. Els pacients SCA presenten concentracions plasmàtiques elevades de BNP atribuïdes a la distensió de la paret ventricular. Existeix poca informació sobre el valor clínic d’aquest marcador cardíac en pacients amb SCA i fracció d’ejecció ventricular esquerra (LVEF) preservada. La demostració que la hipòxia estimula directament la secreció de BNP en cardiomiòcits ventriculars permet formular la hipòtesi que els pacients amb SCA sense insuficiència cardíaca i/o disfunció ventricular presenten concentracions plasmàtiques de BNP elevades, en relació al grau d’hipòxia cel•lular. Mètodes. L’estudi es va realitzar en 1806 pacients amb SCA ingressats de forma consecutiva dins les primeres 24 hores posteriors a l’inici dels símptomes. Es va realitzar un seguiment durant un any de l’aparició d’esdeveniments adversos. RESULTATS. La concentració plasmàtica de BNP en els pacients amb SCA i LVEF preservada va ser superior a l’observada en un grup control d’individus sans. Durant el seguiment, l’aparició d’esdeveniments adversos va ser del 10,0% en els pacients amb LVEF reduïda i del 7,9% en els pacients amb LVEF preservada. Els pacients amb BNP>150 pg/ml van presentar una major probabilitat d’esdeveniments adversos. L’anàlisi estadístic multivariat mostra que la contribució de BNP en la predicció d’esdeveniments adversos es manté desprès d’ajustar en funció de la LVEF. CONCLUSIONS. Els pacients amb SCA i LVEF preservada presenten concentracions plasmàtiques de BNP elevades a l’ingrès, que constitueixen un factor predictor independent de presentar nous episodis de SCA i/o mortalitat., MOLECULAR MECHANISMS OF MYOCARDIAL SECRETION: VENTRICULAR REMODELING AND SECRETION OF B-TYPE NATRIURETIC PEPTIDE. The molecular mechanisms by which myocardial ischemia translates in ventricular remodeling and heart failure remain unclear. In the current thesis it was explored whether hypoxia and proinflammatory factors are specific inducers of matrix remodeling in cardiomyocytes. Adult human ventricular cardiomyocytes (AC16 cells) were incubated at normoxic or hypoxic conditions and stimulated with proinflammatory factors. Matrix remodeling and cellular secretion and gene expression of matrix remodeling factors were analyzed. Results show that hypoxia activates matrix remodeling and induces the production of PIIINP (procollagen III N-terminal propeptide) and inhibits the production of TIMP-1 (tissue inhibitor of metalloproteinase 1). IL1β stimulated the cardiac production of PIIINP, TIMP1 and hyaluronic acid. Results suggest that hypoxia and IL1β may contribute to ventricular dilation and heart failure in ischemic heart diseases. The effect of hypoxia on the cardiac secretion of B-type natriuretic peptid (BNP) was also evaluated. Hypoxia stimulated the protein release and mRNA levels of BNP and VEGF but not ANP in AC16 cells. The analysis of the transcriptional activity of the hypoxia-inducible factor 1 (HIF-1) in nuclear extracts showed that HIF-1 activity was induced under hypoxic conditions. The treatment of AC16 cells with the HIF-1 inhibitor rotenone in hypoxia inhibited BNP and VEGF release. In conclusion, data indicate that hypoxia induces the synthesis and secretion of BNP in human ventricular myocytes, likely through HIF-1-enhanced transcriptional activity. This observed direct effect of hypoxia on BNP secretion in human ventricular myocytes allowed hypothesizing that patients with acute coronary syndromes (ACS) without ventricular dysfunction or heart failure present high plasma levels of BNP related with their degree of cardiac hypoxia. Thus, prognostic significance of BNP plasma levels was evaluated in a cohort of 1806 consecutive patients with ACS admitted within the first 24 hours after the onset of symptoms. The follow up for adverse events was of one year. Plasma levels of BNP in ACS patients with preserved left ventricular ejection fraction (LVEF) were higher than in the control group without ACS. During follow-up, adverse events was 10.0 % in patients with reduced LVEF and 7.9 % in patients with preserved LVEF. Patients with BNP>150 pg/ml presented significantly higher probability of adverse events during follow up. Results show that ACS patients with preserved LVEF present higher BNP levels at admission, which constitute an independent predictor of presenting new ACS and mortality.

Samenvatting van rapport 528901011

In dit rapport wordt ingegaan op de ontwikkelingen in de epidemiologie, etiologie en mogelijkheden voor primaire, secundaire en tertiaire preventie van coronaire hartziekten (CHZ), hartfalen en cerebrovasculaire aandoeningen (CVA) door middel van leefstijlinterventie. Ondanks het feit dat het accent in dit rapport derhalve ligt op de leefstijldeterminanten, blijft ook kennis over de endogene determinanten van belang, aangezien het effect van leefstijlfactoren op het ontstaan en beloop van CHZ en CVA voornamelijk verloopt via de beinvloeding van deze endogene (intermediaire) determinanten. Met betrekking tot de primaire preventie van CHZ, hartfalen en CVA zijn roken, voeding, alcoholgebruik en lichamelijke activiteit belangrijke leefstijldeterminanten. Interventies, gericht op deze determinanten kunnen belangrijke endogene determinanten voor CHZ, hartfalen en CVA (met name serumcholesterol, overgewicht en bloeddruk) gunstig beinvloeden. Gezien de hoge prevalenties van roken, overmatig alcoholgebruik, lichamelijke (in)activiteit en de hoge vetconsumptie in Nederland, biedt interventie op deze determinanten in theorie goede mogelijkheden voor gezondheidswinst. In het verleden zijn programma's ten aanzien van preventie van CHZ en CVA met name gericht geweest op een van de (talrijke) determinanten voor deze aandoeningen. Uit de literatuur blijkt dat de beste resultaten met betrekking tot primaire preventie van CHZ en CVA worden gevonden in multifactoriele programma's, gericht op het verlagen van de niveau's van meerdere factoren tegelijkertijd. Een geintegreerde aanpak van preventie door middel van leefstijlinterventie biedt aanzienlijke mogelijkheden voor gezondheidswinst. Het mechanisme waarlangs omgevingsfactoren, zoals voedingsstoffen, de niveaus van deze endogene determinanten beinvloeden wordt bepaald door verschillende (waaronder genetische) factoren. Dit leidt tot een aanzienlijke variabiliteit in de respons op deze omgevingsfactoren. Het is wenselijk het inzicht in de aard en het effect van deze factoren te vergroten, aangezien dit kan bijdragen aan het opsporen van hoog-risico groepen. Aansluitend bij de consensus-bijeenkomsten ten aanzien van hypercholesterolemie en hypertensie kan worden aanbevolen bij personen met licht verhoogde determinantenniveaus in eerste instantie met behulp van voedingsaanpassingen (beperking van inneming van verzadigd vet, natrium en alcohol) en, indien nodig, gewichtsvermindering te trachten een reductie van de bloeddruk en/of het serumcholesterol te verkrijgen, alvorens over te gaan tot medicamenteuze behandeling. Naast gewichtsreductie past ook regelmatige lichamelijke activiteit in het behandelingsschema. Bij secundaire preventie van CVA en CHZ moet worden gedacht aan het zo vroeg mogelijk herkennen van symptomen bij personen met angina pectoris, TIA of een 'stil' hart- of herseninfarct. Hartfalen is een langzaam voortschrijdende aandoening, die vaak de nasleep is van een hartinfarct. Dit gegeven biedt aanknopingspunten voor secundaire preventie door vroegtijdige onderkenning, gevolgd door adequate behandeling. De bewijslast voor de relatie tussen leefstijlfactoren en het beloop van CHZ, CVA en hartzwakte is kleiner dan die voor het ontstaan van de ziekte, hoofdzakelijk ten gevolge van de (relatief) beperkte informatie over deze relatie in de wetenschappelijke literatuur. De leefstijldeterminanten die een rol spelen bij de etiologie van CHZ, CVA en hartfalen, zijn voor een belangrijk deel ook van belang bij het beloop van de aandoeningen en bieden dus mogelijkheden voor tertiaire preventie. Beinvloeding van het rookgedrag, het verlagen van het serumcholesterol-gehalte, het lichaamsgewicht en de bloeddruk door voedingsaanpassingen en het nastreven van een goede lichamelijke conditie door frequente lichamelijke activiteit, kan de kans op complicaties bij CHZ- en CVA-patienten, zoals een tweede hart- of herseninfarct, verlagen en kan zelfs tot regressie van het atherosclerose-proces leiden. Het huidige rookbeleid, gericht op beperking van het tabaksgebruik en bescherming van de jeugd en de niet-roker, is te vrijblijvend om tot werkelijk resultaat te leiden. Een preventiebeleid ten aanzien van roken zal in verschillende sectoren moeten doordringen om succes te behalen (facetbeleid). De eerstelijns-gezondheidszorg, GGD'en, industrie en wetgevende macht spelen in dat facetbeleid een belangrijke rol. Met betrekking tot het voedingsbeleid is een terughoudendheid merkbaar, waar het de intersectorale aanpak betreft. Dit resulteert tot op dit moment in een slechts traag nerbeterende betrokkenheid van de industrie en minimale vooruitgang in de richtlijnen/wetgeving, bijvoorbeeld ten aanzien van etikettering van voedingsmiddelen. Ook hier is facetbeleid wenselijk. Zo kan de hoge zoutconsumptie in Nederland alleen effectief worden beinvloed als medewerking wordt verkregen van de voedingsmiddelenindustrie, aangezien 85% van de geconsumeerde hoeveelheid zout reeds aanwezig is in het voedingsmiddel, en slechts 15% tijdens het bereiden of aan tafel wordt toegevoegd. Het is opvallend dat in het gezondheidsbeleid nauwelijks aandacht wordt besteed aan het reduceren van lichamelijke inactiviteit. De nieuwste inzichten op het gebied van deze determinant rechtvaardigen een meer stimulerend beleid ten aanzien van lichamelijke activiteit in ons land, waar naar schatting meer dan een derde van de bevolking lichamelijk inactief is in de vrije tijd. Aanbevolen wordt om tot een voorlichtingsplan voor lichamelijke activiteit te komen, vergelijkbaar met het Alcohol Voorlichtings Plan, dat op zowel nationaal als lokaal niveau activiteiten ontplooit, gericht op bewustwording van de problematiek en beinvloeding van de mentaliteit. In het overheidsbeleid ten aanzien van chronisch zieken wordt slechts zeer beperkt aandacht besteed aan de rol die leefstijlfactoren kunnen spelen bij het voorkomen van verergering van de ziekte en de goede mogelijkheden die daarmee ontstaan voor de verbetering van de kwaliteit van leven van de chronisch zieke. Een actiever overheidsbeleid lijkt daarom wenselijk, gezien de mogelijke gezondheidswinst (inclusief verbetering van de kwaliteit van leven) die met tertiaire preventie valt te behalen.

In dit rapport wordt ingegaan op de ontwikkelingen in de epidemiologie, etiologie en mogelijkheden voor primaire, secundaire en tertiaire preventie van coronaire hartziekten (CHZ), hartfalen en cerebrovasculaire aandoeningen (CVA) door middel van leefstijlinterventie. Ondanks het feit dat het accent in dit rapport derhalve ligt op de leefstijldeterminanten, blijft ook kennis over de endogene determinanten van belang, aangezien het effect van leefstijlfactoren op het ontstaan en beloop van CHZ en CVA voornamelijk verloopt via de beinvloeding van deze endogene (intermediaire) determinanten. Met betrekking tot de primaire preventie van CHZ, hartfalen en CVA zijn roken, voeding, alcoholgebruik en lichamelijke activiteit belangrijke leefstijldeterminanten. Interventies, gericht op deze determinanten kunnen belangrijke endogene determinanten voor CHZ, hartfalen en CVA (met name serumcholesterol, overgewicht en bloeddruk) gunstig beinvloeden. Gezien de hoge prevalenties van roken, overmatig alcoholgebruik, lichamelijke (in)activiteit en de hoge vetconsumptie in Nederland, biedt interventie op deze determinanten in theorie goede mogelijkheden voor gezondheidswinst. In het verleden zijn programma's ten aanzien van preventie van CHZ en CVA met name gericht geweest op een van de (talrijke) determinanten voor deze aandoeningen. Uit de literatuur blijkt dat de beste resultaten met betrekking tot primaire preventie van CHZ en CVA worden gevonden in multifactoriele programma's, gericht op het verlagen van de niveau's van meerdere factoren tegelijkertijd. Een geintegreerde aanpak van preventie door middel van leefstijlinterventie biedt aanzienlijke mogelijkheden voor gezondheidswinst. Het mechanisme waarlangs omgevingsfactoren, zoals voedingsstoffen, de niveaus van deze endogene determinanten beinvloeden wordt bepaald door verschillende (waaronder genetische) factoren. Dit leidt tot een aanzienlijke variabiliteit in de respons op deze omgevingsfactoren. Het is wenselijk het inzicht in de aard en het effect van deze factoren te vergroten, aangezien dit kan bijdragen aan het opsporen van hoog-risico groepen. Aansluitend bij de consensus-bijeenkomsten ten aanzien van hypercholesterolemie en hypertensie kan worden aanbevolen bij personen met licht verhoogde determinantenniveaus in eerste instantie met behulp van voedingsaanpassingen (beperking van inneming van verzadigd vet, natrium en alcohol) en, indien nodig, gewichtsvermindering te trachten een reductie van de bloeddruk en/of het serumcholesterol te verkrijgen, alvorens over te gaan tot medicamenteuze behandeling. Naast gewichtsreductie past ook regelmatige lichamelijke activiteit in het behandelingsschema. Bij secundaire preventie van CVA en CHZ moet worden gedacht aan het zo vroeg mogelijk herkennen van symptomen bij personen met angina pectoris, TIA of een 'stil' hart- of herseninfarct. Hartfalen is een langzaam voortschrijdende aandoening, die vaak de nasleep is van een hartinfarct. Dit gegeven biedt aanknopingspunten voor secundaire preventie door vroegtijdige onderkenning, gevolgd door adequate behandeling. De bewijslast voor de relatie tussen leefstijlfactoren en het beloop van CHZ, CVA en hartzwakte is kleiner dan die voor het ontstaan van de ziekte, hoofdzakelijk ten gevolge van de (relatief) beperkte informatie over deze relatie in de wetenschappelijke literatuur. De leefstijldeterminanten die een rol spelen bij de etiologie van CHZ, CVA en hartfalen, zijn voor een belangrijk deel ook van belang bij het beloop van de aandoeningen en bieden dus mogelijkheden voor tertiaire preventie. Beinvloeding van het rookgedrag, het verlagen van het serumcholesterol-gehalte, het lichaamsgewicht en de bloeddruk door voedingsaanpassingen en het nastreven van een goede lichamelijke conditie door frequente lichamelijke activiteit, kan de kans op complicaties bij CHZ- en CVA-patienten, zoals een tweede hart- of herseninfarct, verlagen en kan zelfs tot regressie van het atherosclerose-proces leiden. Het huidige rookbeleid, gericht op beperking van het tabaksgebruik en bescherming van de jeugd en de niet-roker, is te vrijblijvend om tot werkelijk resultaat te leiden. Een preventiebeleid ten aanzien van roken zal in verschillende sectoren moeten doordringen om succes te behalen (facetbeleid). De eerstelijns-gezondheidszorg, GGD'en, industrie en wetgevende macht spelen in dat facetbeleid een belangrijke rol. Met betrekking tot het voedingsbeleid is een terughoudendheid merkbaar, waar het de intersectorale aanpak betreft. Dit resulteert tot op dit moment in een slechts traag nerbeterende betrokkenheid van de industrie en minimale vooruitgang in de richtlijnen/wetgeving, bijvoorbeeld ten aanzien van etikettering van voedingsmiddelen. Ook hier is facetbeleid wenselijk. Zo kan de hoge zoutconsumptie in Nederland alleen effectief worden beinvloed als medewerking wordt verkregen van de voedingsmiddelenindustrie, aangezien 85% van de geconsumeerde hoeveelheid zout reeds aanwezig is in het voedingsmiddel, en slechts 15% tijdens het bereiden of aan tafel wordt toegevoegd. Het is opvallend dat in het gezondheidsbeleid nauwelijks aandacht wordt besteed aan het reduceren van lichamelijke inactiviteit. De nieuwste inzichten op het gebied van deze determinant rechtvaardigen een meer stimulerend beleid ten aanzien van lichamelijke activiteit in ons land, waar naar schatting meer dan een derde van de bevolking lichamelijk inactief is in de vrije tijd. Aanbevolen wordt om tot een voorlichtingsplan voor lichamelijke activiteit te komen, vergelijkbaar met het Alcohol Voorlichtings Plan, dat op zowel nationaal als lokaal niveau activiteiten ontplooit, gericht op bewustwording van de problematiek en beinvloeding van de mentaliteit. In het overheidsbeleid ten aanzien van chronisch zieken wordt slechts zeer beperkt aandacht besteed aan de rol die leefstijlfactoren kunnen spelen bij het voorkomen van verergering van de ziekte en de goede mogelijkheden die daarmee ontstaan voor de verbetering van de kwaliteit van leven van de chronisch zieke. Een actiever overheidsbeleid lijkt daarom wenselijk, gezien de mogelijke gezondheidswinst (inclusief verbetering van de kwaliteit van leven) die met tertiaire preventie valt te behalen.

Samenvatting van rapport 528901011

Coronary artery disease (CAD), also known as ischemic heart disease (IHD) and coronary heart disease (CHD), is caused by the narrowing (stenosis) of one or more coronary arteries, due to atherosclerosis, restricting blood flow and reducing the supply of oxygen to the heart muscle. Transient shortages in blood flow and oxygen lead to angina pectoris and chest pain, which may radiate to the left shoulder, arms, neck, back or jaw. Stable angina symptoms do not tend to progress in intensity over time. More seriously, the rupturing of an atherosclerotic plaque (causing a thrombotic occlusion) and stenosis of the vessel can result in acute myocardial infarction (AMI) due to a critical reduction in the blood supply to the heart muscle (myocardial ischemia). High levels of morbidity and mortality associated with this infarction are a consequence of ischemia. It is vital to promptly re-establish coronary blood flow after an infarction, because sustained ischemic damages and injuries to the heart muscle may lead to sudden death or heart failure. In addition to infarction, acute symptomatic manifestations of ischemic heart disease include unstable angina, and less common conditions such as cardiogenic shock and sudden death (Thygesen, 2007)...

Considerando que a prática de exercício físico com uma intensidade pelo menos moderada melhora a capacidade funcional (Maines et al., 1997; Clara et al., 2002; Olney et al., 2006), a qualidade de vida (Leal et al., 2005; Azevedo & Leal, 2009; Flynn et al., 2009) e diminui os fatores de risco coronários (Maines et al., 1997; Squires & Hamm, 2007; Perk, 2009; Pimenta, 2010), propõe-se com o presente estudo analisar o efeito do exercício físico supervisionado, em fase ambulatório precoce, realizada na comunidade, ao nível da recuperação de doentes cardíacos. Método: Aplicar-se-á um estudo experimental, em doentes cardíacos de ambos os sexos, entre os 28 e os 80 anos. Atribuir-se-á particular ênfase às alterações induzidas pela aplicação do programa de exercício físico nos parâmetros bioquímicos (colesterol total, C-LDL, C-HDL, triglicéridos e glicose), na composição corporal (peso, índice de massa corporal, perímetro da cintura), na capacidade funcional (consumo de oxigénio pico –V02 pico, equivalente metabólico, duplo produto), no nível de atividade física, na ingestão alimentar e na qualidade de vida. O estudo terá uma duração superior a três meses, comparando dois grupos, um grupo submetido ao exercício físico supervisionado (ES) e outro aos cuidados usuais (CU), os quais serão alvo de duas avaliações (inicial e final), avaliando-se a média e o desvio-padrão para todas as variáveis em estudo e recorrendo-se aos testes não paramétricos e paramétricos, para um nível de significância de p< .05. Resultados: Foram elegidos 52 doentes, sendo que 22 participaram no grupo cuidados usuais (CU) e 30 no grupo exercício físico supervisionado (ES), observando-se que o grupo ES apresentou melhorias mais acentuadas quando comparadas com o grupo CU, ao nível dos seguintes indicadores: dispêndio de kcal/semana (+697.22% vs +320.20%); PC (-3.19% vs +5.85%); CT (-23.92% vs -9.29%), C-LDL (-32.52% vs -8.92%); total de kcal/dia ingeridas (-33,31% vs -2.58%); VO2 pico (+30.88% vs -3.57%); qualidade de vida geral (+53.86% vs +2.96%). Conclusão: Concluindo que o exercício físico multicomponente, inserido na fase de ambulatório precoce na comunidade, potencia a recuperação de doentes cardíacos influenciando positivamente os fatores de risco de progressão da doença coronária, a capacidade funcional e a qualidade de vida fundamentais para que o doente possa, pelos seus próprios meios, retomar a sua vida na comunidade., Considering that the physical exercise with at least moderate intensity improves functional capacity (Maines et al., 1997; Clara et al., 2002; Olney et al., 2006), the quality of life (Leal et al., 2005; Leal & Azevedo, 2009; Flynn et al., 2009) and decreases coronary risk factors (Maines et al., 1997; Squires & Hamm, 2007; Perk, 2009; Pepper, 2010), this study proposes to examine the effect of supervised exercise in the early clinical phase held in the community, in the period of heart patients recovery. Method: This will be an experimental study of cardiac patients of both sexes, between 28 and 80 years old. In this study, special emphasis will be put on changes induced by application of physical exercise program in the biochemical parameters (total cholesterol, LDL-C, HDL-C, triglycerides and glucose), body composition (weight, body mass index, perimeter waist), functional capacity (peak oxygen consumption, metabolic equivalent, double product), level of physical activity, food intake and quality of life. The study will last over three months. Two groups undergoing supervised exercise (ES) and usual care (UC) will be compared, which will also be the subjects of two evaluations (initial and final), evaluating the mean and standard for all study variables and resorting to the non-parametric and parametric tests for a significance level of p, Orientador: Jorge Proença

WOS: 000248794000010 PubMed: 17510752 Background Impairment of the release of endothelium and platelet derived-nitric oxide (NO) increases thrombus formation that is rich in platelets in non-ST elevation acute coronary syndromes (NSTE-ACS). Since intracoronary thrombus formation and distal embolization increases risk of myocardial injury, we studied the relationship between NO levels and Tn-I in patients with NSTE-ACS. Methods Nitric oxide and Tn-I levels of 234 consecutive patients with NSTE-ACS were measured from venous samples at admission. The 137 patients whose Tn-I levels were below 0.20 ng/ml grouped as Tn-I negative and 97 patients whose Tn-I levels were equal to and above 0.21 ng/ml were grouped as Tn-I positive. Presence of visible thrombus, degree of flow in Thrombolysis in Myocardial Infarction (TIMI), and morphology of the lesion were evaluated with coronary angiographies. Results Presence of coronary thrombus, impaired TIMI flow, frequency of complex lesions, angina and ST-T changes were more frequent and associated with Tn-I levels in Tn-I positive patients. NO levels were lower in patients who were Tn-I positive, had angina and ST-T changes. NO levels were similar between patients with simple or complex lesions, but lower in patients who had coronary thrombus or TIMI flow grade

OBJETIVO: O objetivo deste estudo é verificar o valor de previsão da angina de peito no diagnóstico da DAC em pacientes portadores de EA, a partir da quinta década de vida. MÉTODOS: A população estudada foi constituída por 186 pacientes consecutivos com EA e idade e" 50 anos, referidos para cirurgia de troca valvar aórtica entre junho de 1989 e setembro de 2004. Cinecoronariografia de rotina foi realizada em todos os pacientes. Cento e um eram homens (54,3%) e 85, mulheres (45,7%), com idade de 66±8 anos. Angina estava presente em 124 pacientes (66,7%). O gradiente máximo transvalvar aórtico foi de 89,4±27,6 mmHg e a área valvar aórtica de 0,59±0,17 cm2. Calculamos a sensibilidade, a especificidade, o valor de previsão positivo e negativo e a razão de verossimilhança positiva da angina na predição da presença de DAC. RESULTADOS: DAC estava presente em 93 pacientes (50%). Dos 124 pacientes com angina, 68 (54,8%) apresentavam DAC; enquanto dos 62 sem angina, 25 apresentavam DAC (40,3%). Portanto, a sensibilidade da angina para DAC foi de 73,1%, a especificidade de 39,7%, valor preditivo positivo de 54,8%, valor preditivo negativo de 59,6% e razão de verossimilhança positiva de 1,6. CONCLUSÃO: A angina de peito não é bom preditor da presença de DAC em pacientes com EA a partir da quinta década de vida. OBJECTIVE: The objective of this study is to evaluate the value of angina pectoris as a predictor of CAD (coronary artery disease) in patients with AS (aortic stenosis) during and beyond the 5th decade of life. METHODS: The study population consisted of 186 consecutive patients with AS and e" 50 years of age, referred for surgical aortic valve replacement (AVR) between June 1989 and September 2004. Routine coronary angiography was performed for all patients. One hundred and one patients were males (54.3%) and 85 were females (45.7%), and the mean age was 66±8 years. One hundred and twenty-four patients (66.7%) had angina. The maximum transvalve gradient was 89.4±27.6 mmHg, and the aortic valve area measured 0.59±0.17 cm2. We calculated the sensitivity, specificity, positive and negative predictive values, as well as the likelihood ratio of a positive test result for angina in predicting the presence of CAD. RESULTS: Ninety-three patients (50%) had CAD. Of the 124 patients with angina, 68 (54.8%) had CAD, whereas of the 62 patients without angina, 25 had CAD (40.3%) (p=0.087). Therefore, the diagnostic sensitivity of angina to detect CAD was 73.1%, specificity was 39.7%, positive predictive value was 54.8%, negative predictive value was 59.6%, and the likelihood ratio of a positive test result was 1.6. CONCLUSION: Angina pectoris is not a good predictor of CAD in patients with AS who are more than 50 years of age.

Background : Cardiogenic shock (CS) after acute myocardial infarction (AMI) develops in 5～10% of patients and it is associated with high mortality. The aim of this study is to assess the predictive factors of mortality for patients with AMI and CS. Methods : Two hundred fifty five AMI patients with CS (the mean age was 66.0±11.0 years, M:F=156:99) out of 1,268 AMI patients who admitted at Chonnam National University Hospital between July 2000 and June 2002 were analyzed according to the clinical characteristics, coronary angiographic findings and MACE during admission and for the 1-year clinical follow-up. Results : Among the enrolled patients, 129 patients survived without MACE (Group I, mean age 64.2±10.6 years, M:F=76:53), and 126 patients had MACE (Group II, mean age 68.1±10.0 years, M:F=80:46) during admission or during the 1-year follow-up period. There were significant differences in age between the Groups I and II (64.2±10.6 vs. 68.1±11.0 years, respectively, p=0.004) and the previous MI history (0 vs. 17.4%, respectively, p

Introduction Few studies have demonstrated the cost burden of cardiovascular events (CVEs) among patients with hyperlipidemia. The primary objective of this study was to determine the mean costs associated with CVEs among patients with hyperlipidemia by follow-up time period. Secondary objectives of this study included characterizing costs by CVE type and coronary heart disease (CHD) risk. Methods This retrospective cohort study used longitudinal claims to calculate payer costs according to CHD risk level and type of CVE, during several follow-up periods (acute and short-term, comprising year 1; plus years 2 and 3). Results There were 193,385 patients with hyperlipidemia with a CVE. Costs in the acute (30-day) period were highest ($22,404) driven by inpatient care (77%). Costs remained high ($15,133 in year 3) with ambulatory care (from 14% in acute to 37% in year 3) and pharmaceutical costs (from 2% in acute to 24% in year 3) representing a greater proportion. After second and third CVEs, acute costs were lower than for the first CVE. But in the post-acute periods, costs were higher after second and third CVEs than after first CVEs. Acute costs varied considerably by type of CVE ($9149 for transient ischemic attack to $54,251 for coronary artery bypass graft; P

Atheromatous and thrombotic embolization during percutaneous coronary revascularization is a feared complication that may cause impaired myocardial reperfusion even with a patent epicardial vessel. The MGuard stent is a cobalt chromium bare metal stent with a porous net attached to its outer surface that has been designed to prevent thrombus fragmentation and distal embolization during stent implantation. This review summarizes the available evidence supporting the use of the MGuard stent in different scenarios such as lesions with high thrombus burden, saphenous vein graft interventions, coronary perforations, or carotid lesions.