- Email: [email protected]
Renopulmonary syndrome, importance of an early diagnosis
430
Letters to the Editor / Med Clin (Barc). 2015;144(9):429–432
4. Kramer MR, Vandijk J, Rosin AJ. Mortality in elderly patients with thermoregulatory failure. Arch Intern Med. 1989;149:1521–3. 5. Epstein E, Anna K. Accidental hypothermia. BMJ. 2006;332:706–9. 6. Hessel EA, Schmer G, Dillard DH. Platelet kinetics during deep hypothermia. J Surg Res. 1980;28:23–4. 7. MacLeod DB, Cortinez LI, Keifer JC, Cameron D, Wright DR, White WD, et al. The desaturation response time of finger pulse oximeters during mild hypothermia. Anaesthesia. 2005;60:65–71. 8. Matsui K, Kurisi S, Nishioka K, Kihara Y. Electrocardiographic changes in accidental hypothermia. Intern Med. 2011;50:1499.
Renopulmonary syndrome, importance of an early diagnosis夽 Síndrome renopulmonar, importancia del diagnóstico precoz Dear Editor, Pulmonary-renal syndrome is a clinical entity characterised by the presence of diffuse alveolar damage and rapidly progressive renal injury, usually in the context of autoimmune disease. Given its potential severity, an adequate diagnostic approach is essential to initiate early treatment for a favourable prognosis and to prevent long-term sequelae (pulmonary fibrosis, chronic renal failure). We present the case of a patient affected by a pulmonary-renal syndrome that was diagnosed in the emergency department, and the importance of the differential diagnosis of this syndrome is analysed. The patient is a 60-year-old male with dyslipidaemia under treatment with statins as well as high blood pressure under treatment with angiotensin receptor antagonists and ß-blockers. He had surgery for prostate adenoma in 2006 and for Peyronie’s disease 2 months before the current consultation. The current disease started 3 months previously in the form of constitutional symptoms with asthenia, a weight loss of 11 kg, evening fever of 38 ◦ C without chills, cough with bloody sputum and progressive dyspnoea during the last month. The patient referred to joint pain in shoulders, elbows and interphalangeal and metacarpophalangeal joints of both hands, and episodes of painful oral ulcers. He did not present Raynaud’s phenomenon or skin lesions. The patient had visited the emergency department 2 weeks earlier with these symptoms and he had been given a chest X-ray that showed a pulmonary infiltrate, and a blood test that showed normocytic normochromic anaemia with haemoglobin 107 g/L and creatinine 1.3 mg/dL, which showed a mild deterioration of renal function in comparison with a preoperative blood test from 4 weeks earlier (haemoglobin 104 g/L). He was treated with amoxicillin/clavulanic acid (875/125 mg/8 h), bronchodilators and prednisone (15 mg/24 h) at a descending dose. He had experienced no improvement, however, so he visited the department again. Physical examination showed: blood pressure 160/80 mmHg, tachypnoea (RR 22), and low-grade fever (37.6 ◦ C). Crackles were heard on auscultation in both lung bases. No signs of heart failure or abdominal or neurological alterations were observed. An arterial blood gas study showed evidence of non-hypercapnic respiratory failure without acidosis, and a general blood test that showed normocytic normochromic anaemia (haemoglobin 95 g/L) and creatinine 1.94 mg/dL. Chest X-ray showed bilateral
夽 Please cite this article as: Mestre-Torres J, Salcedo-Allende MT, Martinez-Valle F, Solans Laqué R. Síndrome renopulmonar, importancia del diagnóstico precoz. Med Clin (Barc). 2015;144:430–431.
Rosa Cámara Gómez ∗ , Agustín Ramos Prol, M. Soledad Navas de Solís, Juan Francisco Merino-Torres Servicio de Endocrinología y Nutrición, Hospital Universitario y Polite´cnico La Fe, Valencia, Spain ∗ Corresponding
author. E-mail address: [email protected] (R. Cámara Gómez).
basal pulmonary infiltrates with no apparent pleural involvement. Given the constitutional symptoms (low-grade fever, dyspnoea, cough and bloody sputum, deterioration of renal function, anaemia and the presence of pulmonary infiltrates), pulmonary-renal syndrome was suspected. We therefore requested an ESR, which was 120 mm/h, and a urine sediment test, which showed haematuria with dysmorphic erythrocytes, representative of glomerular disease, without pyuria or bacteriuria, and urine protein above 500 mg. Three intravenous pulses of 1 g of methylprednisolone were administered while waiting for the serology and culture results and the results of the antineutrophil cytoplasmic antibodies (ANCA) and the anti-glomerular basement membrane antibodies. The differential diagnosis of pulmonary-renal syndrome is wide-ranging, with a different prognosis and treatment depending on the aetiology.1 Therefore, the first diagnostic approach should be done in the emergency department and should include a proper case history, physical examination, and the results of radiological, serological and immunological tests in order to provide patients with the most accurate treatment possible. Among the infectious causes of pulmonary-renal syndrome, we should rule out pneumococcal infections (Legionella and Mycoplasma) through the determination of antigens in urine and serology, which were negative in this patient. Other causes to be considered are immunological diseases, such as Goodpasture syndrome, connective tissue diseases (systemic lupus erythematosus) and systemic vasculitis, especially those associated with ANCA (AAV), essential mixed cryoglobulinaemia and Behc¸et’s disease (BD). In this case, the determination of cryoglobulins was negative, as was the serology for hepatitis B and C viruses, and the patient did not meet the BD diagnostic criteria. The AAV group includes eosinophilic granulomatosis with polyangiitis or Churg-Strauss syndrome, granulomatosis with polyangiitis (GPA) or Wegener granulomatosis, and microscopic polyangiitis (MPA). The first entity seemed unlikely since the patient was not asthmatic, the blood test did not show eosinophilia and this entity is rarely present with pulmonary-renal syndrome. As for GPA, the patient did not have a previous history of sinusitis or a nasal condition, even though all patients present otorhinolaryngological conditions at the start of the disease. MPA could justify all of the patient’s symptoms, as well as the blood test and radiological findings. In our case, the ANCA determination was positive with immunofluorescence (perinuclear pattern [P-ANCA]), and the result was confirmed by ELISA, which was positive for the myeloperoxidase (MPO) antigen at elevated titres (100 L/U, VN < 10). The anti-glomerular basement membrane antibodies were negative. A renal biopsy was performed, which showed focal necrotising glomerulonephritis without deposits in the immunofluorescence study and acute tubular damage with tubular necrosis. With the oriented diagnosis of MPA, treatment with oral prednisone (1 mg/kg weight/day) and pulses of
Letters to the Editor / Med Clin (Barc). 2015;144(9):429–432
cyclophosphamide were administered. Given the progression of the patient’s respiratory failure and anaemia (haemoglobin 75 g/L) in spite of the treatment, 6 sessions of plasmapheresis were added and finally, rituximab was administered, with complete remission of symptoms and normalisation of blood test parameters. The treatment of AAVs varies depending on disease presentation (limited or generalised) and severity. It is divided into 2 phases: remission induction therapy and remission maintenance therapy, in order to reduce the toxic effects of cyclophosphamide as much as possible.2 In the generalised disease, induction treatment includes pulses of corticosteroids followed by oral prednisone at a decreasing rate and pulses of cyclophosphamide. Plasmapheresis is indicated in cases of severe pulmonary haemorrhage.2 Treatment with rituximab has proven to be as efficient as treatment with cyclophosphamide in remission induction, both in patients with severe forms of the disease as well as in those whose disease is refractory to conventional treatment.3 Faced with a patient presenting these characteristics, the emergency department should perform sputum cultures and haemocultures, request serologies for pneumococco, Legionella, Mycoplasma and hepatitis B and C viruses, and determine ANCA, anti-glomerular basement membrane antibodies, antinuclear antibodies, protein analysis, cryoglobulins and levels of complement. The sensitivity and specificity of ANCAs, although variable depending on the technique applied, are highly reliable, the former being 99% for C-ANCA/PR-3 in the case of GPA and 99% for P-ANCA/MPO
Primary cardiovascular prevention with statins in type 2 diabetes mellitus夽 Prevención cardiovascular primaria con estatinas en la diabetes mellitus tipo 2 Dear Editor, Recent publications about primary cardiovascular prevention with statins in diabetic patients aptly discuss whether it is time to change the hypolipidaemic therapeutic strategy for diabetic patients.1 However, there are some extra considerations that we would like to clarify or explain. Firstly, there are discrepancies between the different systems for measuring cardiovascular risk when classifying subjects in different risk categories, as the authors state in SCORE and REGICOR. But it is not right to affirm that the SCORE chart classifies all diabetic patients as high cardiovascular risk patients. When the SCORE2 chart was published, it was already mentioned that, even though diabetes was not included as a variable in the SCORE chart, the risk for diabetic patients was two to four times higher than what was calculated by the chart, depending on whether the subject was male or female. As was correctly stated by the authors of the publication, in order to apply risk functions, it is recommended to use the clinical guidelines that put them in context. The European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) guidelines for the management of dyslipidaemia3 indicate that the risk for diabetic patients is three to five times higher than what was established by SCORE (depending on whether the subject is male or female), in accordance with new analyses of SCORE study data. It is not right to say that the European dyslipidaemia guideline is not based on the SCORE chart. It
夽 Please cite this article as: Cuende JI. Prevención cardiovascular primaria con estatinas en la diabetes mellitus tipo 2. Med Clin (Barc). 2015;144:431–432.
431
in the case of MPA. The specificity is lower, at 73% for C-ANCA/PR-3 and 67% for P-ANCA/MPO.4 References 1. West SC, Arulkumaran N, Ind PW, Pusey CD. Pulmonary-renal syndrome: a life threatening but treatable condition. Postgrad Med J. 2013;89: 274–83. 2. Mukhtyar C, Guillevin L, Cid MC, Dasgupta B, de Groot K, Gross W, et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis. 2009;68:310–7. 3. Jones RB, Tervaert JW, Hauser T, Lugmani R, Morgan MD, Peh CA, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010;15:211–20. 4. Beauvillain C, Delneste Y, Renier G, Jeannin P, Subra JF, Chevailler A. Antineutrophil cytoplasmic autoantibodies: how should the biologist manage them? Clin Rev Allergy Immunol. 2008;35:47–58.
Jaume Mestre-Torres a,∗ , M. Teresa Salcedo-Allende b , Ferran Martinez-Valle a , Roser Solans Laqué a a Servicio de Medicina Interna, Hospital Vall d’Hebron, Barcelona, Spain b Servicio de Anatomía Patológica, Hospital Vall d’Hebron, Barcelona, Spain ∗ Corresponding author. E-mail address: [email protected] (J. Mestre-Torres).
classifies subjects of different cardiovascular risk levels depending on certain clinical circumstances, while also taking into account their SCORE value. It is true that these guidelines classify all type 2 diabetic subjects as very high-risk subjects (as well as type 1 subjects with target organ damage). However, later European guidelines on cardiovascular prevention,4 in which the ESC and EAS also participated, modified these criteria and treat both types of diabetes in the same manner: very high risk when diabetes is associated with other risk factors or target organ damage, and high risk otherwise. These guidelines also use the SCORE chart. It is clear that cardiovascular risk quantification is a controversial issue and that new epidemiological concepts have arisen. The European guidelines on cardiovascular prevention4 are built on the concept of vascular age calculated with SCORE.5 A recent review also builds on the concept of lifetime risk.6 Although risk quantification has improved considerably, there is still a lot to examine for our therapeutic decisions to be based on the best available evidence and for us to use our resources on the patients that will most benefit from them.
References 1. Fábregas LA, González-Clemente JM. Prevención cardiovascular primaria con estatinas en la diabetes mellitus tipo 2: ¿es hora de cambiar de estrategia? Med Clin (Barc). 2014;142:358–9. 2. Conroy R, Pyorala K, Fitzgerald AP, Sans S, Menotti A, de Backer G, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J. 2003;24:987–1003. 3. Reiner Z, Catapano AL, de Backer G, Graham I, Taskinen MR, Wiklund O, et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011;32:1769–818. 4. Perk J, de Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, et al. European guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012;33:1635–701.
Letters to the Editor / Med Clin (Barc). 2015;144(9):429–432
4. Kramer MR, Vandijk J, Rosin AJ. Mortality in elderly patients with thermoregulatory failure. Arch Intern Med. 1989;149:1521–3. 5. Epstein E, Anna K. Accidental hypothermia. BMJ. 2006;332:706–9. 6. Hessel EA, Schmer G, Dillard DH. Platelet kinetics during deep hypothermia. J Surg Res. 1980;28:23–4. 7. MacLeod DB, Cortinez LI, Keifer JC, Cameron D, Wright DR, White WD, et al. The desaturation response time of finger pulse oximeters during mild hypothermia. Anaesthesia. 2005;60:65–71. 8. Matsui K, Kurisi S, Nishioka K, Kihara Y. Electrocardiographic changes in accidental hypothermia. Intern Med. 2011;50:1499.
Renopulmonary syndrome, importance of an early diagnosis夽 Síndrome renopulmonar, importancia del diagnóstico precoz Dear Editor, Pulmonary-renal syndrome is a clinical entity characterised by the presence of diffuse alveolar damage and rapidly progressive renal injury, usually in the context of autoimmune disease. Given its potential severity, an adequate diagnostic approach is essential to initiate early treatment for a favourable prognosis and to prevent long-term sequelae (pulmonary fibrosis, chronic renal failure). We present the case of a patient affected by a pulmonary-renal syndrome that was diagnosed in the emergency department, and the importance of the differential diagnosis of this syndrome is analysed. The patient is a 60-year-old male with dyslipidaemia under treatment with statins as well as high blood pressure under treatment with angiotensin receptor antagonists and ß-blockers. He had surgery for prostate adenoma in 2006 and for Peyronie’s disease 2 months before the current consultation. The current disease started 3 months previously in the form of constitutional symptoms with asthenia, a weight loss of 11 kg, evening fever of 38 ◦ C without chills, cough with bloody sputum and progressive dyspnoea during the last month. The patient referred to joint pain in shoulders, elbows and interphalangeal and metacarpophalangeal joints of both hands, and episodes of painful oral ulcers. He did not present Raynaud’s phenomenon or skin lesions. The patient had visited the emergency department 2 weeks earlier with these symptoms and he had been given a chest X-ray that showed a pulmonary infiltrate, and a blood test that showed normocytic normochromic anaemia with haemoglobin 107 g/L and creatinine 1.3 mg/dL, which showed a mild deterioration of renal function in comparison with a preoperative blood test from 4 weeks earlier (haemoglobin 104 g/L). He was treated with amoxicillin/clavulanic acid (875/125 mg/8 h), bronchodilators and prednisone (15 mg/24 h) at a descending dose. He had experienced no improvement, however, so he visited the department again. Physical examination showed: blood pressure 160/80 mmHg, tachypnoea (RR 22), and low-grade fever (37.6 ◦ C). Crackles were heard on auscultation in both lung bases. No signs of heart failure or abdominal or neurological alterations were observed. An arterial blood gas study showed evidence of non-hypercapnic respiratory failure without acidosis, and a general blood test that showed normocytic normochromic anaemia (haemoglobin 95 g/L) and creatinine 1.94 mg/dL. Chest X-ray showed bilateral
夽 Please cite this article as: Mestre-Torres J, Salcedo-Allende MT, Martinez-Valle F, Solans Laqué R. Síndrome renopulmonar, importancia del diagnóstico precoz. Med Clin (Barc). 2015;144:430–431.
Rosa Cámara Gómez ∗ , Agustín Ramos Prol, M. Soledad Navas de Solís, Juan Francisco Merino-Torres Servicio de Endocrinología y Nutrición, Hospital Universitario y Polite´cnico La Fe, Valencia, Spain ∗ Corresponding
author. E-mail address: [email protected] (R. Cámara Gómez).
basal pulmonary infiltrates with no apparent pleural involvement. Given the constitutional symptoms (low-grade fever, dyspnoea, cough and bloody sputum, deterioration of renal function, anaemia and the presence of pulmonary infiltrates), pulmonary-renal syndrome was suspected. We therefore requested an ESR, which was 120 mm/h, and a urine sediment test, which showed haematuria with dysmorphic erythrocytes, representative of glomerular disease, without pyuria or bacteriuria, and urine protein above 500 mg. Three intravenous pulses of 1 g of methylprednisolone were administered while waiting for the serology and culture results and the results of the antineutrophil cytoplasmic antibodies (ANCA) and the anti-glomerular basement membrane antibodies. The differential diagnosis of pulmonary-renal syndrome is wide-ranging, with a different prognosis and treatment depending on the aetiology.1 Therefore, the first diagnostic approach should be done in the emergency department and should include a proper case history, physical examination, and the results of radiological, serological and immunological tests in order to provide patients with the most accurate treatment possible. Among the infectious causes of pulmonary-renal syndrome, we should rule out pneumococcal infections (Legionella and Mycoplasma) through the determination of antigens in urine and serology, which were negative in this patient. Other causes to be considered are immunological diseases, such as Goodpasture syndrome, connective tissue diseases (systemic lupus erythematosus) and systemic vasculitis, especially those associated with ANCA (AAV), essential mixed cryoglobulinaemia and Behc¸et’s disease (BD). In this case, the determination of cryoglobulins was negative, as was the serology for hepatitis B and C viruses, and the patient did not meet the BD diagnostic criteria. The AAV group includes eosinophilic granulomatosis with polyangiitis or Churg-Strauss syndrome, granulomatosis with polyangiitis (GPA) or Wegener granulomatosis, and microscopic polyangiitis (MPA). The first entity seemed unlikely since the patient was not asthmatic, the blood test did not show eosinophilia and this entity is rarely present with pulmonary-renal syndrome. As for GPA, the patient did not have a previous history of sinusitis or a nasal condition, even though all patients present otorhinolaryngological conditions at the start of the disease. MPA could justify all of the patient’s symptoms, as well as the blood test and radiological findings. In our case, the ANCA determination was positive with immunofluorescence (perinuclear pattern [P-ANCA]), and the result was confirmed by ELISA, which was positive for the myeloperoxidase (MPO) antigen at elevated titres (100 L/U, VN < 10). The anti-glomerular basement membrane antibodies were negative. A renal biopsy was performed, which showed focal necrotising glomerulonephritis without deposits in the immunofluorescence study and acute tubular damage with tubular necrosis. With the oriented diagnosis of MPA, treatment with oral prednisone (1 mg/kg weight/day) and pulses of
Letters to the Editor / Med Clin (Barc). 2015;144(9):429–432
cyclophosphamide were administered. Given the progression of the patient’s respiratory failure and anaemia (haemoglobin 75 g/L) in spite of the treatment, 6 sessions of plasmapheresis were added and finally, rituximab was administered, with complete remission of symptoms and normalisation of blood test parameters. The treatment of AAVs varies depending on disease presentation (limited or generalised) and severity. It is divided into 2 phases: remission induction therapy and remission maintenance therapy, in order to reduce the toxic effects of cyclophosphamide as much as possible.2 In the generalised disease, induction treatment includes pulses of corticosteroids followed by oral prednisone at a decreasing rate and pulses of cyclophosphamide. Plasmapheresis is indicated in cases of severe pulmonary haemorrhage.2 Treatment with rituximab has proven to be as efficient as treatment with cyclophosphamide in remission induction, both in patients with severe forms of the disease as well as in those whose disease is refractory to conventional treatment.3 Faced with a patient presenting these characteristics, the emergency department should perform sputum cultures and haemocultures, request serologies for pneumococco, Legionella, Mycoplasma and hepatitis B and C viruses, and determine ANCA, anti-glomerular basement membrane antibodies, antinuclear antibodies, protein analysis, cryoglobulins and levels of complement. The sensitivity and specificity of ANCAs, although variable depending on the technique applied, are highly reliable, the former being 99% for C-ANCA/PR-3 in the case of GPA and 99% for P-ANCA/MPO
Primary cardiovascular prevention with statins in type 2 diabetes mellitus夽 Prevención cardiovascular primaria con estatinas en la diabetes mellitus tipo 2 Dear Editor, Recent publications about primary cardiovascular prevention with statins in diabetic patients aptly discuss whether it is time to change the hypolipidaemic therapeutic strategy for diabetic patients.1 However, there are some extra considerations that we would like to clarify or explain. Firstly, there are discrepancies between the different systems for measuring cardiovascular risk when classifying subjects in different risk categories, as the authors state in SCORE and REGICOR. But it is not right to affirm that the SCORE chart classifies all diabetic patients as high cardiovascular risk patients. When the SCORE2 chart was published, it was already mentioned that, even though diabetes was not included as a variable in the SCORE chart, the risk for diabetic patients was two to four times higher than what was calculated by the chart, depending on whether the subject was male or female. As was correctly stated by the authors of the publication, in order to apply risk functions, it is recommended to use the clinical guidelines that put them in context. The European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) guidelines for the management of dyslipidaemia3 indicate that the risk for diabetic patients is three to five times higher than what was established by SCORE (depending on whether the subject is male or female), in accordance with new analyses of SCORE study data. It is not right to say that the European dyslipidaemia guideline is not based on the SCORE chart. It
夽 Please cite this article as: Cuende JI. Prevención cardiovascular primaria con estatinas en la diabetes mellitus tipo 2. Med Clin (Barc). 2015;144:431–432.
431
in the case of MPA. The specificity is lower, at 73% for C-ANCA/PR-3 and 67% for P-ANCA/MPO.4 References 1. West SC, Arulkumaran N, Ind PW, Pusey CD. Pulmonary-renal syndrome: a life threatening but treatable condition. Postgrad Med J. 2013;89: 274–83. 2. Mukhtyar C, Guillevin L, Cid MC, Dasgupta B, de Groot K, Gross W, et al. EULAR recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis. 2009;68:310–7. 3. Jones RB, Tervaert JW, Hauser T, Lugmani R, Morgan MD, Peh CA, et al. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010;15:211–20. 4. Beauvillain C, Delneste Y, Renier G, Jeannin P, Subra JF, Chevailler A. Antineutrophil cytoplasmic autoantibodies: how should the biologist manage them? Clin Rev Allergy Immunol. 2008;35:47–58.
Jaume Mestre-Torres a,∗ , M. Teresa Salcedo-Allende b , Ferran Martinez-Valle a , Roser Solans Laqué a a Servicio de Medicina Interna, Hospital Vall d’Hebron, Barcelona, Spain b Servicio de Anatomía Patológica, Hospital Vall d’Hebron, Barcelona, Spain ∗ Corresponding author. E-mail address: [email protected] (J. Mestre-Torres).
classifies subjects of different cardiovascular risk levels depending on certain clinical circumstances, while also taking into account their SCORE value. It is true that these guidelines classify all type 2 diabetic subjects as very high-risk subjects (as well as type 1 subjects with target organ damage). However, later European guidelines on cardiovascular prevention,4 in which the ESC and EAS also participated, modified these criteria and treat both types of diabetes in the same manner: very high risk when diabetes is associated with other risk factors or target organ damage, and high risk otherwise. These guidelines also use the SCORE chart. It is clear that cardiovascular risk quantification is a controversial issue and that new epidemiological concepts have arisen. The European guidelines on cardiovascular prevention4 are built on the concept of vascular age calculated with SCORE.5 A recent review also builds on the concept of lifetime risk.6 Although risk quantification has improved considerably, there is still a lot to examine for our therapeutic decisions to be based on the best available evidence and for us to use our resources on the patients that will most benefit from them.
References 1. Fábregas LA, González-Clemente JM. Prevención cardiovascular primaria con estatinas en la diabetes mellitus tipo 2: ¿es hora de cambiar de estrategia? Med Clin (Barc). 2014;142:358–9. 2. Conroy R, Pyorala K, Fitzgerald AP, Sans S, Menotti A, de Backer G, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J. 2003;24:987–1003. 3. Reiner Z, Catapano AL, de Backer G, Graham I, Taskinen MR, Wiklund O, et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011;32:1769–818. 4. Perk J, de Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, et al. European guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012;33:1635–701.