Consensus document for the use of the Polypill in the secondary prevention of cardiovascular disease. / Documento de consenso del uso clínico de la Polypill en la prevención secundaria del riesgo cardiovascular.

Cardiovascular disease is a chronic disorder which is usually already at an advanced stage when the first symptoms develop. The fact that the initial clinical presentation can be lethal or highly incapacitating emphasizes the need for primary and secondary prevention. It is estimated that the ratio of patients with good adherence to secondary prevention of cardiovascular disease is low and also decreases gradually over time. The Polypill for secondary prevention of cardiovascular disease is the first fixed-dose combination therapy of salicylic acid, atorvastatin and ramipril approved in Spain. The purpose of this consensus document was to define and recommend, through the evidence available in the literature and clinical expert opinion, the impact of treatment adherence in the secondary prevention of cardiovascular disease and the use of the Polypill in daily clinical practice as part of a global strategy including adjustments in patient lifestyle. A RAND/UCLA methodology based on scientific evidence, as well as the collective judgment and clinical expertise of an expert panel was used for this assessment. As a result, a final report of recommendations on the impact of the lack of adherence to treatment of secondary prevention of cardiovascular disease and the effect of using a Polypill in adherence of patients was produced. The recommendations included in this document have been addressed to all those specialists, cardiologists, internists and primary care physicians with competence in prescribing and monitoring patients with high and very high cardiovascular risks.

Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens.

AIMS: To assess the tolerability of initiating/uptitrating sacubitril/valsartan (LCZ696) from 50 to 200 mg twice daily (target dose) over 3 and 6 weeks in heart failure (HF) patients (ejection fraction ≤35%). METHODS AND RESULTS: A 5-day open-label run-in (sacubitril/valsartan 50 mg twice daily) preceded an 11-week, double-blind, randomization period [100 mg twice daily for 2 weeks followed by 200 mg twice daily ('condensed' regimen) vs. 50 mg twice daily for 2 weeks, 100 mg twice daily for 3 weeks, followed by 200 mg twice daily ('conservative' regimen)]. Patients were stratified by pre-study dose of angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker (ACEI/ARB; low-dose stratum included ACEI/ARB-naïve patients). Of 540 patients entering run-in, 498 (92%) were randomized and 429 (86.1% of randomized) completed the study. Pre-defined tolerability criteria were hypotension, renal dysfunction and hyperkalaemia; and adjudicated angioedema, which occurred in ('condensed' vs. 'conservative') 9.7% vs. 8.4% (P = 0.570), 7.3% vs. 7.6% (P = 0.990), 7.7% vs. 4.4% (P = 0.114), and 0.0% vs. 0.8% of patients, respectively. Corresponding proportions for pre-defined systolic blood pressure <95 mmHg, serum potassium >5.5 mmol/L, and serum creatinine >3.0 mg/dL were 8.9% vs. 5.2% (P = 0.102), 7.3% vs. 4.0% (P = 0.097), and 0.4% vs. 0%, respectively. In total, 378 (76%) patients achieved and maintained sacubitril/valsartan 200 mg twice daily without dose interruption/down-titration over 12 weeks (77.8% vs. 84.3% for 'condensed' vs. 'conservative'; P = 0.078). Rates by ACEI/ARB pre-study dose stratification were 82.6% vs. 83.8% (P = 0.783) for high-dose/'condensed' vs. high-dose/'conservative' and 84.9% vs. 73.6% (P = 0.030) for low-dose/'conservative' vs. low-dose/'condensed'. CONCLUSIONS: Initiation/uptitration of sacubitril/valsartan from 50 to 200 mg twice daily over 3 or 6 weeks had a tolerability profile in line with other HF treatments. More gradual initiation/uptitration maximized attainment of target dose in the low-dose ACEI/ARB group.

Update in cardiology: vascular risk and cardiac rehabilitation.

As in other fields, understanding of vascular risk and rehabilitation is constantly improving. The present review of recent epidemiological update shows how far we are from achieving good risk factor control: in diet and nutrition, where unhealthy and excessive societal consumption is clearly increasing the prevalence of obesity; in exercise, where it is difficult to find a balance between benefit and risk, despite systemization efforts; in smoking, where developments center on programs and policies, with the electronic cigarette seeming more like a problem than a solution; in lipids, where the transatlantic debate between guidelines is becoming a paradigm of the divergence of views in this extensively studied area; in hypertension, where a nonpharmacological alternative (renal denervation) has been undermined by the SYMPLICITY HTN-3 setback, forcing a deep reassessment; in diabetes mellitus, where the new dipeptidyl peptidase-4 and sodium-glucose cotransporter type 2 inhibitors and glucagon like peptide 1 analogues have contributed much new information and a glimpse of the future of diabetes treatment, and in cardiac rehabilitation, which continues to benefit from new information and communication technologies and where clinical benefit is not hindered by advanced diseases, such as heart failure. Our summary concludes with the update in elderly patients, whose treatment criteria are extrapolated from those of younger patients, with the present review clearly indicating that should not be the case.

[Diagnosis and treatment of familial hypercholesterolemia in Spain: consensus document]. / Diagnóstico y tratamiento de la hipercolesterolemia familiar en España: documento de consenso.

Familial hypercholesterolemia (FH) is a common genetic disorder, clinically manifested since birth, and associated with very high levels of plasma LDL-cholesterol (LDL-c), xanthomas, and premature coronary heart disease. Its early detection and treatment reduces coronary morbidity and mortality. Despite effective treatment being available, FH is under-diagnosed and under-treated. Identification of index cases and cascade screening using LDL-c levels and genetic testing are the most cost-effective strategies for detecting new cases and starting early treatment. Long-term treatment with statins has decreased the vascular risk to the levels of the general population. LDL-c targets are < 130 mg/dL for children and young adults, <100mg/dL for adults, and < 70 mg/dL for adults with known coronary heart disease or diabetes. Most patients do not to reach these goals, and combined treatments with ezetimibe or other drugs may be necessary. When the goals are not achieved with the maximum tolerated drug treatment, a reduction ≥ 50% in LDL-c levels can be acceptable. Lipoprotein apheresis can be useful in homozygous, and in treatment-resistant severe heterozygous, cases. This Consensus Paper gives recommendations on the diagnosis, screening, and treatment of FH in children and adults, and specific advice to specialists and general practitioners with the objective of improving the clinical management of these patients, in order to reduce the high burden of coronary heart disease.

[Diagnosis and treatment of familial hypercholesterolemia in Spain: Consensus document]. / Diagnóstico y tratamiento de la hipercolesterolemia familiar en España: documento de consenso.

Familial hypercholesterolemia (FH) is a common genetic disorder, clinically manifested since birth, and associated with very high levels of plasma LDL-cholesterol (LDL-c), xanthomas, and premature coronary heart disease. Its early detection and treatment reduces coronary morbidity and mortality. Despite effective treatment being available, FH is under-diagnosed and under-treated. Identification of index cases and cascade screening using LDL-c levels and genetic testing are the most cost-effective strategies for detecting new cases and starting early treatment. Long-term treatment with statins has decreased the vascular risk to the levels of the general population. LDL-c targets are <130mg/dL for children and young adults, <100mg/dL for adults, and <70mg/dL for adults with known coronary heart disease or diabetes. Most patients do not to reach these goals, and combined treatments with ezetimibe or other drugs may be necessary. When the goals are not achieved with the maximum tolerated drug treatment, a reduction ≥50% in LDL-c levels can be acceptable. Lipoprotein apheresis can be useful in homozygous, and in treatment-resistant severe heterozygous, cases. This Consensus Paper gives recommendations on the diagnosis, screening, and treatment of FH in children and adults, and specific advice to specialists and general practitioners with the objective of improving the clinical management of these patients, in order to reduce the high burden of coronary heart disease.

FHL2 expression and variants in hypertrophic cardiomyopathy.

Based on evidence that FHL2 (four and a half LIM domains protein 2) negatively regulates cardiac hypertrophy we tested whether FHL2 altered expression or variants could be associated with hypertrophic cardiomyopathy (HCM). HCM is a myocardial disease characterized by left ventricular hypertrophy, diastolic dysfunction and increased interstitial fibrosis and is mainly caused by mutations in genes coding for sarcomeric proteins. FHL2 mRNA level, FHL2 protein level and I-band-binding density were lower in HCM patients than control individuals. Screening of 121 HCM patients without mutations in established disease genes identified 2 novel (T171M, V187L) and 4 known (R177Q, N226N, D268D, P273P) FHL2 variants in unrelated HCM families. We assessed the structural and functional consequences of the nonsynonymous substitutions after adeno-associated viral-mediated gene transfer in cardiac myocytes and in 3D-engineered heart tissue (EHT). Overexpression of FHL2 wild type or nonsynonymous substitutions in cardiac myocytes markedly down-regulated α-skeletal actin and partially blunted hypertrophy induced by phenylephrine or endothelin-1. After gene transfer in EHTs, force and velocity of both contraction and relaxation were higher with T171M and V187L FHL2 variants than wild type under basal conditions. Finally, chronic phenylephrine stimulation depressed EHT function in all groups, but to a lower extent in T171M-transduced EHTs. These data suggest that (1) FHL2 is down-regulated in HCM, (2) both FHL2 wild type and variants partially protected phenylephrine- or endothelin-1-induced hypertrophy in cardiac myocytes, and (3) FHL2 T171M and V187L nonsynonymous variants induced altered EHT contractility. These findings provide evidence that the 2 novel FHL2 variants could increase cardiac function in HCM.

Update in cardiology: vascular risk and cardiac rehabilitation.

Cardiovascular disease develops in a slow and subclinical manner over decades, only to manifest suddenly and unexpectedly. The role of prevention is crucial, both before and after clinical appearance, and there is ample evidence of the effectiveness and usefulness of the early detection of at-risk individuals and lifestyle modifications or pharmacological approaches. However, these approaches require time, perseverance, and continuous development. The present article reviews the developments in 2013 in epidemiological aspects related to prevention, includes relevant contributions in areas such as diet, weight control methods (obesity is now considered a disease), and physical activity recommendations (with warnings about the risk of strenuous exercise), deals with habit-related psychosocial factors such as smoking, provides an update on emerging issues such as genetics, addresses the links between cardiovascular disease and other pathologies such as kidney disease, summarizes the contributions of new, updated guidelines (3 of which have recently been released on topics of considerable clinical importance: hypertension, diabetes mellitus, and chronic kidney disease), analyzes the pharmacological advances (largely mediocre except for promising lipid-related results), and finishes by outlining developments in the oft-neglected field of cardiac rehabilitation. This article provides a briefing on controversial issues, presents interesting and somewhat surprising developments, updates established knowledge with undoubted application in clinical practice, and sheds light on potential future contributions.

Patients with cardiac disease: Changes observed through last decade in out-patient clinics.

AIM: To describe current profile of patients with cardiovascular disease (CVD) and assessing changes through last decade. METHODS: Comparison of patients with established CVD from two similar cross-sectional registries performed in 1999 (n = 6194) and 2009 (n = 4639). The types of CVD were coronary heart disease (CHD), heart failure (HF) and atrial fibrillation (AF). Patients were collected from outpatient clinics. Investigators were 80% cardiologist and 20% primary care practitioners. Clinical antecedents, major diagnosis, blood test results and medical treatments were collected from all patients. RESULTS: An increase in all risk factors, except for smoking, was observed; a 54.4% relative increase in BP control was noted. CHD was the most prevalent CVD but HF and AF increased significantly, 41.5% and 33.7%, respectively. A significant reduction in serum lipid levels was observed. The use of statins increased by 141.1% as did all cardiovascular treatments. Moreover, the use of angiotensin-renin system inhibitors in patients with HF, beta-blockers in CHD patients or oral anticoagulants in AF patients increased by 83.0%, 80.3% and 156.0%, respectively (P < 0.01). CONCLUSION: The prevalence of all cardiovascular risk factors has increased in patients with CVD through last decade. HF and AF have experienced the largest increases.

Update in cardiology: Vascular risk and cardiac rehabilitation.

Atherosclerotic cardiovascular disease remains the major cause of premature death in developed and developing countries. Nevertheless, surveys show that most patients still do not achieve the lifestyles, risk factor levels, and therapeutic targets recommended in primary and secondary prevention. The present update reflects the most recent novelties in risk classification and estimation of risk and documents the latest changes in fields such as smoking, diet and nutrition, physical activity, lipids, hypertension, diabetes, and cardiovascular rehabilitation, based on experimental trials and population-based observational studies.

Attitude and efficacy of cardiologists with respect to smoking in patients after acute coronary syndromes.

INTRODUCTION AND OBJECTIVES: Smoking is one of the most prevalent risk factors in acute coronary syndrome patients. The aim of this study was to assess the attitudes of cardiologists to the smoking habits of these patients METHODS: A prospective multicenter registry of acute coronary syndrome patients. The primary endpoint was defined as smoking abstinence and the secondary endpoint as the incidence of all-cause mortality or nonfatal myocardial infarction. RESULTS: The study population included 715 patients; 365 were current smokers. During follow-up (median, 375.0 days [interquartile range, 359.3-406.0 days]), 110 patients (30.6%) received smoking cessation support (19.7% at hospital discharge and 37.6% at month 3), specialized units and varenicline being the strategies most frequently used. No clinical differences were observed between patients who received smoking cessation support and those who did not, except for a higher prevalence of previous coronary heart disease in those who received support. In the multivariate analysis, the only variable independently associated with receiving smoking cessation support was previous coronary heart disease (odds ratio=3.16; 95% confidence interval, 1.64-6.11; P<.01). The abstinence rate was 72.3% at month 3 and 67.9% at 1 year; no differences were observed between the patients who received smoking cessation support and those who did not. During follow-up, a nonsignificant trend toward a lower incidence of the secondary endpoint was observed among the patients who were smokers at the time of acute coronary syndrome and who achieved abstinence (P=.07). CONCLUSIONS: Use of smoking cessation support strategies is limited in acute coronary syndrome patients and is more widespread among those with previous coronary heart disease.

[Clinical features and hospital complications of patients with acute coronary syndromes according to smoking habits]. / Características clínicas y evolución hospitalaria de los pacientes con síndrome coronario agudo en función del tabaquismo.

BACKGROUND AND OBJECTIVE: Current smoking patients with acute coronary syndromes (ACS) seem to have better prognosis during hospital stay. The objective of this study was to describe the clinical characteristics and complications of patients with ACS according to smoking habits. PATIENTS AND METHODS: Observational, multicentre and nationwide registry. Primary endpoint was hospital mortality and secondary endpoint was the combination of mortality, angina or heart failure. RESULTS: 825 ACS patients were collected. Current smokers were 413 (50.1%) and their mean age was 12 years lower than the rest and also had lower prevalence of risk factors or previous cardiovascular disease. Complications and mortality were similar according to smoking habits. Multivariate adjusted analysis identified age > 75 (OR: 12.80, 95% CI 1.35-41.44; p=0.03) and GFR < 60 ml/min/1.73 m(2) (OR: 10.20, 95% CI 1.06-97.92; p=0.04) independently associated with mortality; age > 75 (OR: 1.72, 95% CI 1.03-2.84; p=0.04), GFR < 60 ml/min/1.73 m(2) (OR: 1.76, 95% CI 1.08-2.91; p=0.023) and current smoking (OR: 1.05, 95% CI 1.01-1.10; p=0.02) were independently associated with the combined end-point. Elderly current smokers patients had the highest mortality rate (19.0%) followed by elderly former smokers patients (5.8%). CONCLUSIONS: Current smoker patients with ACS have lower mean age and have similar hospital complications.

[Factors associated with uncontrolled hypertension in patients with and without cardiovascular disease]. / Factores asociados a la falta de control de la hipertensión arterial en pacientes con y sin enfermedad cardiovascular.

INTRODUCTION AND OBJECTIVES: Hypertension is one of the most prevalent and poorly controlled risk factors, especially in patients with established cardiovascular disease (CVD). The aim of this study was to describe the rate of blood pressure (BP) control and related risk factors. METHODS: Multicenter, cross-sectional and observational registry of patients with hypertension recruited from cardiology and primary care outpatient clinics. Controlled BP defined as <140/90 mmHg. RESULTS: 55.4% of the 10 743 patients included had controlled BP and these had a slightly higher mean age. Patients with uncontrolled BP were more frequently male, with a higher prevalence of active smokers, obese patients, and patients with diabetes. The rate of controlled BP was similar in patients with or without CVD. Patients with uncontrolled BP had higher levels of blood glucose, total cholesterol, low density lipoproteins and uric acid. Patients with uncontrolled BP were receiving a slightly higher mean number of antihypertensive drugs compared to patients with controlled BP. Patients with CVD were more frequently receiving a renin-angiotensin-aldosterone axis inhibitor: 83.5% vs. 73.2% (P<.01). Multivariate analysis identified obesity and current smoking as independently associated with uncontrolled BP, both in patients with or without CVD, as well as relevant differences between the two groups on other factors. CONCLUSIONS: Regardless of the presence of CVD, 55% of hypertensive patients had controlled BP. Lifestyle and diet, especially smoking and obesity, are independently associated with lack of BP control. Full English text available from: www.revespcardiol.org.

[Antialdosteronic agents: their role in heart failure]. / Fármacos antialdosterónicos: su papel en la insuficiencia cardíaca.

Antialdosteronic treatment is used again in heart failure. It pursues the neurohormonal blockage of the final effector of the renin-angiotensin axis. Employed agents include espironolactone and, more recently, eplerenone (which lacks the adverse effects of the former such as gynecomastia). They have beneficial effects both in advanced heart failure (NYHA class III or IV) and heart insufficiency appearing after myocardial infarction. It remains to be demonstrated if they are also effective in less advanced chronic heart insufficiency (NYHA class II) and diastolic cardiac failure, though several ongoing studies are testing this benefit. Trials with antialdosteronics have shown improvements in overall mortality, even when patients were already receiving full therapy including ACEIs and, lastly, beta-blockers. The limitation of antialdosteronics is hyperkaliemia, which occurs more frequently in the general population than in patients enrolled in clinical trials, since the former is an elderly population with greater comorbility and submitted to less controls. Therefore, antialdosteronic treatment cannot be administered in some cases (especially if there is a renal function impairment) and a careful monitoring of the serum ionnograme is mandatory.

Estatinas postinfarto. Un beneficio incuestionable. Una estrategia terapÚutica perfeccionable / Postinfarction statins. An unquestionable benefit. A therapeutic strategy that can be improved

Atherosclerotic disease is etiopathogenically related to the presence of hypercholesterolemia. Physicians have never had until now a generation of lipid-lowering drugs with a comparable degree of efficacy, potency and safety as statins. The most explored field with statins has been the post myocardial infarction period, since this type of patients is at high risk of new cardiovascular events and, as a consequence, can obtain a marked benefit from intervention. Accordingly, three large-scale clinical trials with statins have conclusively demonstrated a significant reduction in cardiovascular events and in mortality after myocardial infarction. Nevertheless, although there is convincing evidence that statins should be implemented after myocardial infarction, there are still a number of relevant questions open and under study. The first of them is the value of the so-called pleiotropic properties of statins (additional properties independent from cholesterol lowering), so important for plaque stabilization. In addition, there is uncertainty about how early treatment with statins has to be started after the acute phase. Another point we do not know is the goal of lipid intervention (the level of total or LDL-cholesterol to be achieved). In fact, there is still a debate on whether patients with average levels of cholesterol or even with low levels are to treated. Finally, but related to the previous question, it would be very interesting to determine whether high doses of statins, are necessary or can low doses be equally efficacious. In conclusion, statins are a landmark in cholesterol-lowering interventions after myocardial infarction. Probably, the majority of survivors should be treated. At present, active research is focused on delineating more precisely the manner in which these drugs are to be used to prolong life in these patients.

Caracterización morfológica de la miocardiopatía hipertrófica mediante SPECT miocárdico de perfusión: análisis cuantitativo / Morfologic characterization of hypertrophic myocardiopathy by perfusion myocardial SPECT: quantitative analysis

OBJETIVO: Estudiar las posibilidades de la tomogammagrafía miocárdica de perfusión (SPECT: single photon emission computed tomography) en la valoración cuantitativa del grosor ventricular izquierdo de la miocardiopatía hipertrófica (MH) y en su caracterización morfológica. MATERIAL Y METODOS: Se estudiaron dos grupos. El grupo MH estuvo formado por 70 pacientes consecutivos (53 ñ 13 años; 30 mujeres) diagnosticados de MH por ecocardiograma-Doppler (36 con obstrucción dinámica). El grupo control lo formaron 20 individuos normal (46 ñ 11 años; 7 mujeres). A todos se les practicó una tomogammagrafía miocárdica de esfuerzo-reposo (protocolo de un solo día) con 99mTc-tetrofosmina. En las imágenes de reposo del eje corto se realizaron las medidas del grosor parietal en el centro de las regiones septal, anterior, lateral e inferior, en dos niveles de corte (apical y medial). Del análisis estadístico de las 8 regiones (4 apicales y 4 mediales), se determinaron los valores medios y las desviaciones estándar del grosor parietal de ambos grupos para cada región. Con la finalidad de establecer los límites de normalidad para cada región se determinaron los valores de las desviaciones estándar en el grupo control y se compararon con la región correspondiente de los pacientes con MH. RESULTADOS: Las regiones septal y anterior fueron las más frecuentemente comprometidas en los pacientes con MH. Según las diferentes asociaciones de segmentos hipertróficos se pudieron observar hasta 13 variedades morfológicas diferentes de MH. CONCLUSIONES: Estos resultados muestran que el SPECT miocárdico cuantitativo es posible realizar una caracterización morfológica de la miocardiopatía hipertrófica hasta en 13 variantes según las diferentes localizaciones de la hipertrofia. Las regiones septal y anterior son las que se afectan con mayor frecuencia