The clinical value of ß-blockers in patients with stable angina.

Stable angina, one manifestation of chronic coronary syndrome (CCS), is characterised by intermittent episodes of insufficient blood supply to the myocardium, provoking symptoms of myocardial ischaemia, particularly chest pain. These attacks usually occur during exercise or stress. Anti-ischaemic drugs are the mainstay of pharmacologic management of CCS with symptoms of angina. ß-blockers reduce heart rate and myocardial contractility, thus reducing myocardial oxygen consumption. These drugs have been shown to ameliorate the frequency of anginal attacks and to improve exercise capacity in these patients. Current management guidelines include ß-blockers as a first-line management option for most patients with CCS and symptoms of myocardial ischaemia, alongside dihydropyridine calcium channel blockers (CCB). The presence of comorbid angina and heart failure is a strong indication for starting with a ß-blocker. ß-blockers are also useful in the management of angina symptoms accompanied by a high heart rate, hypertension (with or without a renin-angiotensin-aldosterone-system [RAS] blocker or CCB), or microvascular angina (with a RAS blocker and a statin). A ß-blocker is not suitable for a patient with low heart rate (<50 bpm), although use of a ß-blocker may be supported by a pacemaker if the ß-blocker is strongly indicated) and should be used at a low dose only in patients with low blood pressure.

Prevalence of Combined Lipid Abnormalities in Brazilian Adolescents and Its Association with Nutritional Status: Data from the Erica Study.

Background: Cardiovascular diseases are the leading cause of death in Brazil and worldwide. The growing incidence of obesity in children and adolescents and its association with lipid abnormalities may worsen this scenario, mainly in developing countries where obesity has reached epidemic levels. Dyslipidemias have several patterns, and the combination of some lipid abnormalities may have higher atherogenic potential. Objectives: To evaluate the prevalence of single or multiple combined lipid abnormalities in adolescents and its association with nutritional status assessed by body mass index. Methods: Data were obtained from the Study of Cardiovascular Risks in Adolescents (ERICA), a school-based, national representative study with Brazilian adolescents between 12 and 17 years of age. Adolescents whose lipid profiles were available were included, and lipid abnormalities were defined as LDL-C ≥ 100 mg/dL, HDL-C < 45 mg/dL, and tryglicerides (TG) ≥ 100 mg/dL. We assessed the prevalence of single or combined lipid abnormalities and correlated this nutritional status with body mass index of low weight, normal, overweight, and obesity. Results: A total of 38,069 adolescents were included, with more than 24,000 of them presenting at least one lipid abnormality (64.7%), and 3.7% showing alterations in all of them. The most prevalent combination was high TG with low HDL-C levels. The higher the BMI, the more lipid abnormalities were found. Conclusions: In this large and representative sample of Brazilian adolescents, the majority had at least one lipid abnormality. Higher BMI was associated with a higher prevalence of combined lipid abnormalities. Highlights: - There is a high prevalence of Brazilian adolescents with dyslipidemias.- BMI was associated with a higher prevalence of combined lipid abnormalities.- BMI can be considered as an indicator of the diagnosis of dyslipidemia in adolescents.

Efeito cardiovascular superior do modelo periodizado para prescrição de exercícios comparado ao convencional em coronariopatas / Superior cardiovascular effect of the periodized model for prescribed exercises as compared to the conventional one in coronary diseases

O exercício físico melhora a sobrevida e a qualidade de vida de pacientes coronarianos, mas a maneira ideal de prescrevê-lo é ainda controversa. Criar um modelo periodizado para prescrição de exercícios para pacientes coronarianos e compará-lo com o modelo convencional. Randomização de 62 pacientes coronarianos em tratamento farmacológico em dois grupos: treinamento convencional, não periodizado (GNP, n = 33) e periodizado (GP, n = 29). Os dois grupos foram submetidos aos mesmos exercícios durante as 36 sessões do programa, mas prescritos de maneira diferente. Todos os pacientes foram submetidos à seguinte avaliação: consulta médica admissional, teste de esforço cardiopulmonar, teste de 1 repetição máxima (1RM) e avaliação da composição corporal. O VO2 pico melhorou nos dois grupos, embora de maneira mais efetiva no GP (4% versus 1,7%, p < 0,001). Além disso, a capacidade funcional do GP aumentou em 13%, tendo havido significativa redução no percentual de gordura corporal (2,1%, p < 0,005) e no peso corporal (1,9 kg, p < 0,005). A força muscular nos dois grupos melhorou como diagnosticado pelo teste de 1RM para seis diferentes grupos musculares (quádriceps, isquiotibiais, bíceps, tríceps braquial, peitoral e grande dorsal), mas sem diferença significativa entre os grupos, tendo os dois modelos a mesma eficiência. O presente estudo mostrou que a periodização do treinamento de pacientes cardíacos pode melhorar a capacidade cardiorrespiratória e reduzir a porcentagem de gordura corporal mais efetivamente do que o modelo convencional

Physical exercise improves the survival and quality of life of coronary patients, but the ideal way of prescribing these exercises is still controversial. To create a new periodized model for the prescription of exercises for coronary patients and compare it with a conventional model. 62 coronary patients under pharmacological treatment were randomized into two groups: conventional (NPG, n = 33) and periodized (PG, n = 29) training. The two groups were submitted to the same exercises during the 36 sessions making up the program, but prescribed in different ways. All patients underwent an evaluation consisting of: medical admission consultancy, cardiopulmonary endurance testing, 1 maximum repetition test (1MR) and body composition evaluation. The VO2 peak improved in both groups, although more effectively in the PG (4% against 1.7%, p < 0.001). In addition, the functional capacity of this group improved by 13%, and there was a significant reduction in the percent body fat (2.1%, p < 0.005) and body weight (1.9 kg, p < 0.005). The muscle strength of both groups improved as diagnosed by the 1RM test for six different muscle groups (quadriceps, hamstrings, brachial biceps, brachial triceps, pectoral and large dorsal), and showed no significant difference between the groups, evidencing that the two models had the same efficiency. The present study showed that periodization of the training of cardiac patients can improve their cardiorespiratory capacity and reduce the percent body fat more effectively than the conventional one

Prevalence of high cholesterol levels suggestive of familial hypercholesterolemia in Brazilian adolescents: Data from the study of cardiovascular risk in adolescents.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder with an estimated worldwide prevalence ranging from 1 in 200 individuals to 1 in 500 individuals in its heterozygous form. Individuals with FH exhibit high low-density lipoprotein cholesterol (LDLc) levels from birth, which leads to premature cardiovascular events. In Brazil, like in most countries around the world, FH is considered a public health problem but remains underdiagnosed and undertreated. OBJECTIVE: The aim of this study was to evaluate the prevalence of LDLc or non-high-density lipoprotein cholesterol (non-HDLc) levels suggestive of FH among Brazilian adolescents. METHODS: The Study of Cardiovascular Risk in Adolescents (ERICA) was a nationwide, school-based, cross-sectional study that assessed the prevalence of cardiovascular risk factors in approximately 75,000 adolescents between 12 and 17 years old. Data were analyzed according to sex, age, type of school (public or private), and geographic regions of Brazil. Adolescents with untreated fasting LDLc levels of 160 mg/dL or higher or non-HDLc levels of 190 mg/dL or higher were suspected to have FH. We also evaluated the prevalence of LDLc levels of 190 mg/dL or higher, which is highly suggestive of a diagnosis of FH in this age group. RESULTS: A total of 38,069 adolescents were evaluated; more than half (59.9%) were female and most (74%) attended public schools. The prevalence of LDLc levels of 160 mg/dL or higher or non-HDLc levels of 190 mg/dL or higher among the adolescents was 0.49% (95% confidence interval: 0.34-0.71; n = 209). Moreover, 0.12% of the adolescents (95% confidence interval: 0.04-0.34; n = 44) had LDLc levels of 190 mg/dL or higher. We estimate that approximately 100,000 (1 in 200) Brazilian adolescents aged 12 to 17 years are suspected to have FH on the basis of LDLc and non-HDLc levels. CONCLUSION: We identified a significant prevalence of cholesterol levels suggestive of FH among Brazilian adolescents. Further evaluation is needed to confirm the diagnoses among the students. Our results reinforce the importance of universal screening as a critical tool for early diagnosis and treatment of FH.

World Heart Federation Cholesterol Roadmap.

BACKGROUND: The World Heart Federation has undertaken an initiative to develop a series of Roadmaps. OBJECTIVES: The aim of these is to promote development of national policies and health systems approaches and identify potential roadblocks on the road to effective prevention, detection and management of cardiovascular disease (CVD) in low-and middle-income countries (LMIC), and strategies for overcoming these. This Roadmap focuses on elevated blood cholesterol, a leading risk factor for myocardial infarction, stroke, and peripheral arterial disease. METHODS: Through a review of published guidelines and research papers, and consultation with a committee composed of experts in clinical management of cholesterol and health systems research in LMIC, this Roadmap identifies (1) key interventions for primordial, primary and secondary prevention of CVD through detection, treatment, and management of elevated cholesterol and familial hypercholesterolemia (FH); (2) gaps in implementation of these interventions (knowledge-practice gaps); (3) health system roadblocks to treatment of elevated cholesterol in LMIC; and (4) potential strategies for overcoming these. RESULTS: Despite strong evidence of the importance of cholesterol levels in primary or secondary prevention of CVD, and the effectiveness of statin therapy for cholesterol lowering and reduction of CVD risk, gaps exist in the detection, treatment, and management of high cholesterol globally. Some potential roadblocks include poor access to laboratory facilities or trained professionals for cholesterol management, low awareness of FH among the general population and health professionals, unaffordability of statins for patient households, and low awareness of the importance of persistent adherence to lipid-lowering medication. Potential solutions include point-of-care testing, provision of free or subsidized lipid-lowering medication, and treatment adherence support using text message reminders. CONCLUSIONS: Known effective strategies for detection, treatment, and management of elevated cholesterol and FH exist, but there are barriers to their implementation in many low-resource settings. Priorities for health system intervention should be identified at the national level, and the feasibility and effectiveness of proposed solutions should be assessed in specific contexts. Many solutions proposed in this Roadmap may apply to other cardiovascular conditions and present opportunities for integration of CVD care in LMIC.

Passive immunization with monoclonal IgM antibodies against phosphorylcholine reduces accelerated vein graft atherosclerosis in apolipoprotein E-null mice.

Phosphorylcholine (PC) headgroup is one of the neoantigens exposed by LDL oxidation that can elicit an immune response. Active immunization with Streptococcus pneumoniae, which bears PC on its cell wall, reduced atherosclerosis in hypercholesterolemic mice and this effect was attributed to an immune response to PC. In this study we tested the hypothesis that passive immunization with a monoclonal anti-PC IgM antibody can be athero-protective in a murine model of native aortic and vein graft atherosclerosis. Inferior vena cava from 16-week-old donor male apoE-null mice was grafted into right carotid artery of age-matched male recipient apoE-null mice. Anti-PC IgM titers were evaluated before and 4 weeks after surgery. For the immunization protocol, a separate group of mice received weekly intraperitoneal injection of monoclonal anti-PC IgM (400 microg) for 4 weeks, starting the day of surgery. Controls received PBS or pooled polyclonal IgM. Anti-PC IgM titres significantly increased at 4 weeks following surgery. Passive immunization with anti-PC IgM reduced vein graft plaque size and neointimal thickness resulting in a larger luminal area; in addition immunization reduced the inflammatory cell content of the plaques. There was no significant effect on the established native aortic atherosclerotic lesions. Immunization did not affect circulating cholesterol levels. Taken together our data suggest that passive immunization with anti-PC IgM significantly reduces vein graft lesion size with less inflammatory phenotype without affecting cholesterol levels, indicating an athero-protective immune response to PC. Lack of effect on established native aortic lesions may have been due to short duration of therapy and/or reduced efficacy in established lesions as compared to evolving lesions of vein graft atherosclerosis.

Differential effects of apolipoprotein A-I-mimetic peptide on evolving and established atherosclerosis in apolipoprotein E-null mice.

BACKGROUND: Apolipoprotein (apo) A-I and apoA-I-mimetic peptides showed promise to prevent atherosclerosis development. Using a bypassed vein graft model in apoE-null mice, we evaluated the effects of oral or intraperitoneal administration of an apoA-I-mimetic peptide on evolving atherosclerotic lesions in the vein graft and compared such effects on the established atherosclerotic lesions in aortic sinus in the same mice. METHODS AND RESULTS: We used apoE-null mice in which a segment of inferior vena cava was grafted into the right carotid artery at 16 weeks of age. Native aortic atherosclerotic lesions (established atherosclerosis) and vein-graft atherosclerotic lesions (evolving atherosclerosis) were assessed 4 weeks after daily oral (0.3 mg/mL) or intraperitoneal (50 microg in 200 microL saline) administration of an apoA-I-mimetic peptide, D4F. Mice receiving saline or water without D4F served as controls. Both oral and intraperitoneal administration of D4F reduced vein-graft atherosclerotic (evolving lesions) plaque size by 43% and 42%, plaque lipid by 70% and 49%, and macrophage immunoreactivity by 63% and 62%, respectively, compared with controls. In contrast, D4F had no effect on the native aortic sinus atherosclerotic lesions (established lesions). CONCLUSIONS: Oral and intraperitoneal administration of the apoA-I-mimetic peptide D4F significantly reduced rapidly evolving atherosclerotic lesions in vein grafts but not established atherosclerotic lesions in aortic sinus. These observations suggest that the type of atherosclerotic lesions and the time of initiation during the course of lesion evolution modulate the beneficial effects of apoA-I-mimetic peptides on atherosclerosis.