Atherogenic Dyslipidaemia 2019. Consensus document of the Atherogenic Dyslipidaemia Group of the Spanish Arteriosclerosis Society | Clínica e Investigación en Arteriosclerosis (English Edition)

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Documento de consenso del Grupo de Dislipidemia Aterogénica de la Sociedad Española de Arteriosclerosis" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 951 "Ancho" => 1638 "Tamanyo" => 102146 ] ] "descripcion" => array:1 [ "en" => "apoB: apolipoprotein B; non-HDL-c: non-HDL cholesterol (total cholesterol minus HDL cholesterol); HDLc: high density lipoprotein cholesterol; CVR: cardiovascular risk; TG: triglycerides." ] ] ] "textoCompleto" => "Definition of atherogenic dyslipidaemiaAtherogenic dyslipidaemia is characterized by an increase in the plasma levels of total triglycerides (TG) and a fall in the cholesterol of high density lipoproteins (HDLc). Together with both of these lipid alterations which define atherogenic dyslipidaemia, we find an increase in TG-rich lipoprotein and carriers of apolipoprotein B (apoB) usually with a moderate increase, sometime with close to normal values, of the concentration of low density lipoproteins (LDLc), with a predominance of small dense LDL particles.<a class="elsevierStyleCrossRef" href="#bib0150">1</a>Atherogenic dyslipidaemia is highly important as it is associated with different diseases which are currently widespread in the general population. These diseases are accompanied by a high degree of cardiovascular risk (CVR), including being overweight (37%), obesity (17%), diabetes (14%) and metabolic syndrome (30%).<a class="elsevierStyleCrossRefs" href="#bib0155">2,3</a> Moreover, atherogenic dyslipidaemia is in itself an indicator of high CVR in subjects with diabetes; it is therefore associated with a higher risk of silent myocardial ischemia or angiographic coronary disease in patients with type 2 diabetes and LDLc levels <130mg/dL.<a class="elsevierStyleCrossRef" href="#bib0165">4</a>The fact is that there is a high prevalence of atherogenic dyslipidaemia in the Spanish population: it is present in 34% of diabetics, 21% of high-risk patients with controlled LDLc, and from 21% to 34% of patients with a history of vascular disease in some location (coronary, cerebral or the peripheral arteries).<a class="elsevierStyleCrossRef" href="#bib0170">5</a>DiagnosisAtherogenic dyslipidaemia is characterized by hypertriglyceridaemia, which results from the increase in all of the TG-rich lipoproteins and their residual particles, and by moderate elevation of LDL; i.e., the set of atherogenic lipoproteins which contain apoB. All of these atherogenic lipoproteins can be quantified in terms of non-HDL cholesterol (non-HDL-c) or apoB. On the other hand, there is a reduction in HDLc.Together with these alterations, the presence of an increase in small dense LDL particles, calculated indirectly by the TG/HDLc index, and the increase in atherogenic coefficients, especially TC/HDLc, form the set of the findings in this dyslipidaemia,<a class="elsevierStyleCrossRef" href="#bib0175">6</a> as shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Cardiovascular risk and therapeutic objectivesNon-HDL-c essentially represents the sum of the cholesterol of the lipoproteins that contain apoB, i.e., the atherogenic lipoproteins which are able to form deposits on the arterial wall. Due to this, it has been recommended that for patients with atherogenic dyslipidaemia the most appropriate therapeutic parameter is non-HDL-c or apoB, as both parameters correlate better with CVR than LDLc.<a class="elsevierStyleCrossRef" href="#bib0180">7</a>Non-HDL-c has been shown to be a solid factor in CVR, so that in habitual clinical practice is may substitute apoB, as it is more economical and easier to calculate. This is because it is only necessary to subtract HDLc from total cholesterol, and these analytical parameters are available in all of the clinical laboratories in hospitals. The current recommendation is to measure apoB when this is clinically possible, especially in cases with atherogenic dyslipidaemia and its associated alterations, hypertriglyceridaemia, obesity, metabolic syndrome, diabetes and clinical cardiovascular disease.<a class="elsevierStyleCrossRef" href="#bib0185">8</a>The scientific evidence for the association between high levels of LDLc and increased risk of cardiovascular disease is strong and incontrovertible. Nevertheless, even with suitable control of LDLc, there remains a considerable percentage of subjects who maintain a high vascular risk that is attributable to other lipid alterations, such as hypertriglyceridaemia and a fall in HDLc. The highest CVR is found when alterations coexist in all 3 lipid fractions: raised LDLc and triglycerides, and lower HDLc.<a class="elsevierStyleCrossRef" href="#bib0190">9</a>In their meta-analysis of 62,154 patients included in 8 studies, Anderson et al.<a class="elsevierStyleCrossRef" href="#bib0190">9</a> showed that non-HDL-c has a better correlation with CVR than LDLc; additionally, the subjects who attained therapeutic objectives for LDLc but not for non-HDL-c had a 32% increase in risk compared with those who achieved both objectives. Similar data were supplied by Boekholdt et al.<a class="elsevierStyleCrossRef" href="#bib0195">10</a>Likewise, a recent study showed that progression of the atheroma plaque was more closely associated with concentrations of non-HDL-c than it was with those of LDLc. The lowest levels of non-HDL-c and TG therefore showed a significant association with plaque regression through the different CVR categories.<a class="elsevierStyleCrossRef" href="#bib0200">11</a>We therefore had to consider that in patients with atherogenic dyslipidaemia the main risk predictor and thus the main target for control is non-HDL-c.<a class="elsevierStyleCrossRef" href="#bib0205">12</a> On the other hand, it has been established that the CVR in subjects with atherogenic dyslipidaemia is double or triple that of the general population and, in the majority of cases, they have a high CVR.<a class="elsevierStyleCrossRefs" href="#bib0210">13,14</a>Calculation of non-HDL-c based on total cholesterol minus HDLc is the CVR-dependent objective: its values have been set as those of the LDLc target plus 30mg/dL.Consequently, the non-HDL-c and apoB goal will be: in moderate CVR <130mg/dL and <100mg/dL, respectively; in high CVR <100mg/dL and <80mg/dL, respectively, and in very high CVR <85mg/dL and <65mg/dL, respectively (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Secondary objectives: triglycerides and HDLcHypertriglyceridaemia is an independent CVR factor: concentrations of TG <150mg/dL are considered optimum.<a class="elsevierStyleCrossRef" href="#bib0220">15</a> Thus although the therapeutic objective has not been clearly established, it may be considered to stand at <150mg/dL.Plasma HDLc concentrations <40mg/dL in men and <45mg/dL in women are also considered to be independent CVR factors, so that it would be desirable to achieve figures higher than these.<a class="elsevierStyleCrossRefs" href="#bib0220">15,16</a>The PROVE IT-TIMI 22 study was a prospective study of 4162 patients hospitalised due to acute coronary syndrome and treated with statins (pravastatin or atorvastatin). Analysis of its results showed that patients whose LDLc remained under 70mg/dL obtained a 16% reduction in recurring cardiovascular episodes, while the group that reduced LDLc (<70mg/dL) and TG below 150mg/dL achieved a fall in cardiovascular episodes of 28%.<a class="elsevierStyleCrossRef" href="#bib0230">17</a>Consensus points in the clinical evaluation of atherogenic dyslipidaemiaBased on the available data and most important clinical evidence, the key points in connection with atherogenic dyslipidaemia associated CVR are:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">–Hypertriglyceridaemia is an independent CVR factor that is exacerbated in the presence of high levels of LDLc or low levels of HDLc. It is one of the key elements in the residual vascular risk caused by lipids.</li><li class="elsevierStyleListItem" id="lsti0010">–To evaluate overall CVR it is indispensible to determine TG and HDLc.</li><li class="elsevierStyleListItem" id="lsti0015">–The most useful markers when evaluating the risk attributable to atherogenic dyslipidaemia are non-HDL-c (at a level higher than LDLc) or apoB and TG. TG are a marker of residual lipoproteins that are rich in TG and, indirectly, of the cholesterol of these lipoproteins. Dividing the concentration of TG by 5 if levels are expressed in mg/dL or by 2.2 if they are expressed in mmol/L allows us to calculate TG-rich residual lipoprotein cholesterol. A level >30mg/dL (>0.3mmol/L) indicates that there is an excess of the said cholesterol.</li><li class="elsevierStyleListItem" id="lsti0020">–Non-HDL-c is the appropriate therapeutic target for controlling CVR in patients with atherogenic dyslipidaemia. Although apoB is the ideal marker as it is correlated well with non-HDL-c, it may not be generally available for routine use. Both parameters are highly stable for calculating CVR in cases of atherogenic dyslipidaemia and its associated alterations.</li></ul>The treatment of atherogenic dyslipidaemiaAtherogenic dyslipidaemia is an extremely important entity that clearly contributes to the residual risk after treatment with statins. This dyslipidaemia is under-diagnosed, under-treated and under-controlled. It is particularly relevant in patients at high CVR and those with abdominal obesity, metabolic syndrome and diabetes.<a class="elsevierStyleCrossRef" href="#bib0235">18</a>It is necessary to consider the treatment of this entity based on the available scientific evidence, to improve how it is treated as well as patient adherence.Lifestyle changesThe first measures to reduce CVR in all patients are a healthy diet, regular physical exercise and smoking cessation.The Mediterranean diet, with a reduction in total calorie intake in case of weight gain or abdominal obesity, is accompanied by clear cardiovascular benefits and increased longevity. As well as its beneficial effects on the lipid profile, it also has positive effects on hypertension and hyperglycaemia. The consumption of alcohol must be moderated or avoided in cases of moderate to severe hypertriglyceridaemia.Aerobic physical exercise too is primordial in atherogenic dyslipidaemia and in the prevention and treatment of metabolic syndrome, hyperglycaemia, diabetes and cardiovascular disease.Pharmacological treatmentAs the majority of patients with atherogenic dyslipidaemia are at high or very high risk of cardiovascular disease, different lipid lowering drugs must be combined with lifestyle changes.StatinsTreatment with statins will start, selecting the type and dose necessary to achieve the therapeutic objective in terms of the required reduction in LDLc. The benefits of treatment with statins are well-known, and they have been clearly proven. A reduction of 1mmol/L (approximately 39mg/dL) in LDLc is associated with a 21% fall in the incidence of severe cardiovascular episodes and a 23% fall in coronary accidents.<a class="elsevierStyleCrossRef" href="#bib0240">19</a>It is relevant that treatment with low power statins during 10 years in subjects at low CVR has been associated with a 23% reduction in non-mortal episodes of myocardial infarct. However, this reduction amounted to 53% when more powerful statins were used, including a significant reduction in cardiovascular events.<a class="elsevierStyleCrossRefs" href="#bib0245">20,21</a> Statins are the first pharmacological treatment to be used in patients with atherogenic dyslipidaemia, as a fall of 1mmol/L (39mg/dL) in residual cholesterol is also associated with an important reduction in cardiovascular events, similar to what has been observed with the reduction in LDLc.<a class="elsevierStyleCrossRef" href="#bib0255">22</a>FibratesOnce treatment with statins has achieved the target LDLc level, there is still an unacceptably high risk of cardiovascular events due to the presence of the main components of atherogenic dyslipidaemia (hypertriglyceridaemia and reduced HDLc). Administering fibrates under these conditions corrects these lipid alterations and has additional cardiovascular benefits. Fibrates have been shown to be beneficial in primary and secondary prevention studies as well as in the diabetic population, above all in the subgroups with atherogenic dyslipidaemia or one of its components, with a fall of 28–30% in cardiovascular events.<a class="elsevierStyleCrossRefs" href="#bib0260">23,24</a>In the case of fibrate contraindication or intolerance and with raised TG, omega-3 fatty acids may be beneficial in these patients.<a class="elsevierStyleCrossRef" href="#bib0270">25</a>Fibrate-induced lipid changes are explained by modifications in the expressivity of several genes involved in lipid metabolism, through α receptors activated by peroxisome proliferation, with a fall in TG of 20–50%, in LDLc of 5–20% (with a reduction in small and dense LDL particles) and an increase in HDLc of from 5% to 20%. These effects depend on basal concentrations<a class="elsevierStyleCrossRef" href="#bib0200">11</a> and are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>.<a class="elsevierStyleCrossRef" href="#bib0275">26</a><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Fenofibrate is the safest fibrate for association with a statin: adding it achieves a stronger cholesterol-lowering effect and control of non-HDL-c, TG and HDLc.Unlike what occurs with gemfibrozil, the combination of fenofibrate and a statin has shown an excellent safety profile in all of the clinical studies, which include a large number of patients and prolonged treatment. Additionally, the effects of the fenofibrate–statin association on raised muscle or hepatic enzymes, or on the transitory increase in creatinine, do not differ from what has been observed in monotherapy regimes, so that the reversibility of its effects can be checked.The FIRST study, which compared the effects of fibrates in subjects treated with atorvastatin on intima-media carotid artery thickness, found a significant reduction in the group treated with fibrates, especially the subjects with triglycerides >170mg/dL and in those with greater arterial intima-media thickness in the basal situation.<a class="elsevierStyleCrossRef" href="#bib0280">27</a>Another work that supports the benefit of treatment with fenofibrate together with statins in subjects with metabolic syndrome is a prospective 5-year study with a large number of patients. This showed a reduction in the combined objective (ischemic coronary disease, cerebral ischemic disease and cardiovascular death) in 36% of the group with added fenofibrate in comparison with the placebo.<a class="elsevierStyleCrossRef" href="#bib0285">28</a>The main clinical evidence for treatment with fenofibrate is shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>.<a class="elsevierStyleCrossRefs" href="#bib0225">16,29</a><elsevierMultimedia ident="tbl0020"></elsevierMultimedia>Extralipid effects of fenofibrateThe results of clinical studies with fenofibrate indicate that as well as changes in the lipid profile, it has other protective vascular effects such as increasing the expression of nitric oxide and reducing oxidative stress. Fibrates have an anti-inflammatory action as they attenuate the production of inflammatory cytokines. Fenofibrate complements this anti-inflammatory action by significantly reducing reactive C protein, the CD40 ligand, monocyte-1 chemotactic protein and the macrophage stimulant factor. It also reduces the plasma concentrations of fibrinogen by up to 20%, thrombin-antithrombin complexes and plasminogen-1 activator inhibitor. Another important extralipid effect is the slowing down of the progression of diabetic retinopathy, independently of glycemic and lipid control. Additionally, these studies indicate that fenofibrate plays a protective role in nephropathy and diabetic neuropathy.<a class="elsevierStyleCrossRef" href="#bib0290">29</a>The algorithm shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> is based on these facts, for the treatment of atherogenic dyslipidaemia and the control of its associated CVR.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Consensus points in the treatment of atherogenic dyslipidaemia<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025">–Changes in lifestyle, a lipid reducing diet with appropriate calories for weight control, physical exercise and smoking cessation are highly effective in all patients and are the first step in managing atherogenic dyslipidaemia.</li><li class="elsevierStyleListItem" id="lsti0030">–Following changes in lifestyle, statins are the effective and safe initial treatment for the prevention of cardiovascular risk.</li><li class="elsevierStyleListItem" id="lsti0035">–Patients with hypertriglyceridaemia and low HDLc, that is, with atherogenic dyslipidaemia, would benefit from combined statin–fenofibrate therapy.</li><li class="elsevierStyleListItem" id="lsti0040">–Clinical practice guides and the European Medicines Agency indicate fenofibrate for the treatment of mixed hyperlipidaemia together with a statin when TG and non-HDLc are not properly controlled.</li><li class="elsevierStyleListItem" id="lsti0045">–The evidence for the clinical benefit and safety of the statin–fenofibrate association is solid. The combination of both drugs in a single tablet simplifies the dosage and may aid adherence over the long term.</li></ul>Conflict of interestsThis is a Spanish Arteriosclerosis Society workgroup and it receives financial support from Mylan." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Definition of atherogenic dyslipidaemia" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Diagnosis" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Cardiovascular risk and therapeutic objectives" ] 3 => array:2 [ "identificador" => "sec0020" "titulo" => "Secondary objectives: triglycerides and HDLc" ] 4 => array:2 [ "identificador" => "sec0025" "titulo" => "Consensus points in the clinical evaluation of atherogenic dyslipidaemia" ] 5 => array:3 [ "identificador" => "sec0030" "titulo" => "The treatment of atherogenic dyslipidaemia" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Lifestyle changes" ] 1 => array:3 [ "identificador" => "sec0040" "titulo" => "Pharmacological treatment" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Statins" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Fibrates" ] ] ] ] ] 6 => array:2 [ "identificador" => "sec0055" "titulo" => "Extralipid effects of fenofibrate" ] 7 => array:2 [ "identificador" => "sec0060" "titulo" => "Consensus points in the treatment of atherogenic dyslipidaemia" ] 8 => array:2 [ "identificador" => "sec0065" "titulo" => "Conflict of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Ascaso JF, Millán J, Hernández-Mijares A, Blasco M, Brea Á, Díaz Á, et al. Dislipidemia aterogénica 2019. Documento de consenso del Grupo de Dislipidemia Aterogénica de la Sociedad Española de Arteriosclerosis. Clin Investig Arterioscler. 2020;32:120–125." ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 951 "Ancho" => 1638 "Tamanyo" => 102146 ] ] "descripcion" => array:1 [ "en" => "apoB: apolipoprotein B; non-HDL-c: non-HDL cholesterol (total cholesterol minus HDL cholesterol); HDLc: high density lipoprotein cholesterol; CVR: cardiovascular risk; TG: triglycerides." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "HDLc: high density lipoprotein cholesterol; LDLc: low density lipoprotein cholesterol; LDL: low density lipoproteins; TG: triglycerides." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>150mg/dL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HDLc \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><40mg/dL in men and <45mg/dL in women \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">LDLc \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>100mg/dL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Non-HDL-c \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>130mg/dL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TC/HDLc \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>5 in men and >4.5 in women \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Small dense LDL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TG/HDLc >2 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2310909.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Atherogenic dyslipidaemia." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "ApoB: apolipoprotein B; non-HDL-c: cholesterol bound to atherogenic lipoproteins (total cholesterol minus high density lipoprotein cholesterol); HDLc: high density lipoprotein cholesterol; TC: total cholesterol; CV: cardiovascular; DM: diabetes mellitus; DM1: type 1 diabetes mellitus; PAD: peripheral arterial disease; CKD: chronic kidney disease; CVD: cardiovascular disease; eFG: estimated glomerular filtrate; FCVR: cardiovascular risk factor; W: men; FH: family hypercholesterolemia; AMI: acute myocardial infarct; TOL: target organ lesion; W: women; AP: arterial pressure; ACS: acute coronary syndrome; SCORE: European societies risk of cardiovascular death score; TG: triglycerides; TIA: transitory cerebral ischemia." "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Primary objectives</th></tr><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Primary objective \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Non-HDL-c (mg/dL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ApoB (mg/dL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Moderate CV risk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><130 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><100 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DM1 <35 years or DM2 <50 years, duration <10 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SCORE 1–4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">High CV risk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><80 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 severe FCVR (TC >310mg/dL, LDLc >190mg/dL, AP ≥180/110mmHg) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FH without another FCVR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DM without TOL, with ≥10 years evolution or with 1 FCVR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CKD eFG 30–59mL/min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SCORE 5–9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="3" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"></td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Very high CV risk \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><65 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Documented DCV: clinical (ACS, AMI, angina, revascularisation, ictus or TIA, PAD) or unmistakeable image (plaque >50% with any im technique) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">DM with lesion target organ or 1 of the 3 major FCVR or DM1 >20 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CKD-eFG <30mL/min \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">SCORE ≥10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FH with CVD or with 1 major FCVR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2310906.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Secondary objectives \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TG (mg/dL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HDLc (mg/dL) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">After achieving the primary objective \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><150 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">>40H>45W \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2310907.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Lipid objectives in atherogenic dyslipidaemia." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "apoA-I: apolipoprotein A-I; apoA-II: apolipoprotein A-II; apoC-III: apolipoprotein C-III; apoA-V: apolipoprotein A-V; CETP: cholesterol esters transport protein; HDL: high density lipoproteins; LDL: low density lipoproteins; LPL: lipoprotein lipase; TG: triglycerides; VLDL: very low density lipoproteins." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mechanisms \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Reduction in TG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Increasing lipolysis (increasing LPL activity, the synthesis of apoA-V and reducing apoC-III synthesis)Increasing plasma clearing of TG-rich lipoproteinsReducing the availability of fatty acids (reducing synthesis de novo and increasing oxidation) and therefore the synthesis of TG and VLDL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Increasing HDL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Increasing the synthesis of apoA-I and apoA-IIReducing CETP activity and therefore the transfer of cholesterol to the VLDL and of TG to the HDL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Changes in LDL particle phenotype \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Inducing a change of small dense LDL particles, especially atherogenic ones, to ones that are larger and less dense \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2310908.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Lipid effects of fibrates." ] ] 4 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Non-HDL-c: cholesterol bound to atherogenic lipoproteins (total cholesterol minus high density lipoprotein cholesterol); HDLc: high density lipoprotein cholesterol; LDLc: low density lipoprotein cholesterol; CVD: cardiovascular disease; TG: triglycerides." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Consider treatment with fibrates for the primary prevention of CVD in patients at high cardiovascular risk and for secondary prevention in those with atherogenic dyslipidaemia, with normal LDLc or non-HDL-c, and in general after treatment with a statin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Evidence class BRecommendation IIb \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">In diabetic patients under treatment with statins, for primary as well as secondary prevention, fenofibrate will be used if TG levels are higher than 200mg/dL with or without low HDLc \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Evidence class BRecommendation IIa \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">The combination of fenofibrate–statin is the safest of the fibrate-statin combinations which are available, due to the lower probability of severe adverse effects. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Evidence class ARecommendation IIa \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Fenofibrate brings about changes in the size of LDL and HDL particles, improving endothelial dysfunction and has anti-inflammatory effects, reducing thrombogenesis and playing a protective role in diabetic retinopathy. \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Evidence class CRecommendation: consider for use \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2310905.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Evidence for treatment with fibrates." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:29 [ 0 => array:3 [ "identificador" => "bib0150" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of dyslipidemia in the metabolic syndrome: recommendations of the Spanish HDL-Forum" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. 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Atherogenic Dyslipidaemia 2019. Consensus document of the Atherogenic Dyslipidaemia Group of the Spanish Arteriosclerosis Society

Dislipidemia aterogénica 2019. Documento de consenso del Grupo de Dislipidemia Aterogénica de la Sociedad Española de Arteriosclerosis

Juan F. Ascasoa,

Corresponding author

ascaso@uv.es

Corresponding author.

, Jesús Millánb, Antonio Hernández-Mijaresc, Mariano Blascod, Ángel Breae, Ángel Díazf, Juan Pedro-Botetg, Xavier Pintóh, SEA Atherogenic Dyslipidemia Working Group

a Universitat de Valencia, CIBERDEM, INCLIVA, Valencia, Spain

b Unidad de Lípidos, Servicio de Medicina Interna, Hospital General Universitario Gregorio Marañón, Facultad de Medicina Universidad Complutense, Madrid, Spain

c Universitat de Valencia, Valencia, Spain

d Centro de Salud Delicias Sur, Área Sanitaria III, Zaragoza, Spain

e Unidad de Lípidos, Servicio de Medicina Interna, Hospital San Pedro, Logroño, Spain

f Centro de Salud de Bembibre, Universidad de León, León, Spain

g Unidad de Lípidos y Riesgo Vascular, Servicio Endocrinología y Nutrición, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain

h Servicio de Medicina Interna, Hospital de Bellvitge, CIBERobn, Fipec, Universidad de Barcelona, IBIDELL, Barcelona, Spain

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the presence of an increase in small dense LDL particles&#44; calculated indirectly by the TG&#47;HDLc index&#44; and the increase in atherogenic coefficients&#44; especially TC&#47;HDLc&#44; form the set of the findings in this dyslipidaemia&#44;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">6</span></a> as shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Cardiovascular risk and therapeutic objectives</span><p id="par0030" class="elsevierStylePara elsevierViewall">Non-HDL-c essentially represents the sum of the cholesterol of the lipoproteins that contain apoB&#44; i&#46;e&#46;&#44; the atherogenic lipoproteins which are able to form deposits on the arterial wall&#46; Due to this&#44; it has been recommended that for patients with atherogenic dyslipidaemia the most appropriate therapeutic parameter is non-HDL-c or apoB&#44; as both parameters correlate better with CVR than LDLc&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Non-HDL-c has been shown to be a solid factor in CVR&#44; so that in habitual clinical practice is may substitute apoB&#44; as it is more economical and easier to calculate&#46; This is because it is only necessary to subtract HDLc from total cholesterol&#44; and these analytical parameters are available in all of the clinical laboratories in hospitals&#46; The current recommendation is to measure apoB when this is clinically possible&#44; especially in cases with atherogenic dyslipidaemia and its associated alterations&#44; hypertriglyceridaemia&#44; obesity&#44; metabolic syndrome&#44; diabetes and clinical cardiovascular disease&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The scientific evidence for the association between high levels of LDLc and increased risk of cardiovascular disease is strong and incontrovertible&#46; Nevertheless&#44; even with suitable control of LDLc&#44; there remains a considerable percentage of subjects who maintain a high vascular risk that is attributable to other lipid alterations&#44; such as hypertriglyceridaemia and a fall in HDLc&#46; The highest CVR is found when alterations coexist in all 3 lipid fractions&#58; raised LDLc and triglycerides&#44; and lower HDLc&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">9</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In their meta-analysis of 62&#44;154 patients included in 8 studies&#44; Anderson et al&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">9</span></a> showed that non-HDL-c has a better correlation with CVR than LDLc&#59; additionally&#44; the subjects who attained therapeutic objectives for LDLc but not for non-HDL-c had a 32&#37; increase in risk compared with those who achieved both objectives&#46; Similar data were supplied by Boekholdt et al&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">10</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Likewise&#44; a recent study showed that progression of the atheroma plaque was more closely associated with concentrations of non-HDL-c than it was with those of LDLc&#46; The lowest levels of non-HDL-c and TG therefore showed a significant association with plaque regression through the different CVR categories&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">11</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">We therefore had to consider that in patients with atherogenic dyslipidaemia the main risk predictor and thus the main target for control is non-HDL-c&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">12</span></a> On the other hand&#44; it has been established that the CVR in subjects with atherogenic dyslipidaemia is double or triple that of the general population and&#44; in the majority of cases&#44; they have a high CVR&#46;<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">13&#44;14</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Calculation of non-HDL-c based on total cholesterol minus HDLc is the CVR-dependent objective&#58; its values have been set as those of the LDLc target plus 30<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Consequently&#44; the <span class="elsevierStyleItalic">non-HDL-c and apoB goal</span> will be&#58; in moderate CVR &#60;130<span class="elsevierStyleHsp" style=""></span>mg&#47;dL and &#60;100<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; respectively&#59; in high CVR &#60;100<span class="elsevierStyleHsp" style=""></span>mg&#47;dL and &#60;80<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; respectively&#44; and in very high CVR &#60;85<span class="elsevierStyleHsp" style=""></span>mg&#47;dL and &#60;65<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; respectively &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Secondary objectives&#58; triglycerides and HDLc</span><p id="par0070" class="elsevierStylePara elsevierViewall">Hypertriglyceridaemia is an independent CVR factor&#58; concentrations of TG &#60;150<span class="elsevierStyleHsp" style=""></span>mg&#47;dL are considered optimum&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">15</span></a> Thus although the therapeutic objective has not been clearly established&#44; it may be considered to stand at &#60;150<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Plasma HDLc concentrations &#60;40<span class="elsevierStyleHsp" style=""></span>mg&#47;dL in men and &#60;45<span class="elsevierStyleHsp" style=""></span>mg&#47;dL in women are also considered to be independent CVR factors&#44; so that it would be desirable to achieve figures higher than these&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">15&#44;16</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">The PROVE IT-TIMI 22 study was a prospective study of 4162 patients hospitalised due to acute coronary syndrome and treated with statins &#40;pravastatin or atorvastatin&#41;&#46; Analysis of its results showed that patients whose LDLc remained under 70<span class="elsevierStyleHsp" style=""></span>mg&#47;dL obtained a 16&#37; reduction in recurring cardiovascular episodes&#44; while the group that reduced LDLc &#40;&#60;70<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; and TG below 150<span class="elsevierStyleHsp" style=""></span>mg&#47;dL achieved a fall in cardiovascular episodes of 28&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Consensus points in the clinical evaluation of atherogenic dyslipidaemia</span><p id="par0085" class="elsevierStylePara elsevierViewall">Based on the available data and most important clinical evidence&#44; the key points in connection with atherogenic dyslipidaemia associated CVR are&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">&#8211;</span></span><p id="par0090" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Hypertriglyceridaemia is an independent CVR factor that is exacerbated in the presence of high levels of LDLc or low levels of HDLc&#46; It is one of the key elements in the residual vascular risk caused by lipids&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">&#8211;</span></span><p id="par0095" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">To evaluate overall CVR it is indispensible to determine TG and HDLc&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">&#8211;</span></span><p id="par0100" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The most useful markers when evaluating the risk attributable to atherogenic dyslipidaemia are non-HDL-c &#40;at a level higher than LDLc&#41; or apoB and TG&#46; TG are a marker of residual lipoproteins that are rich in TG and&#44; indirectly&#44; of the cholesterol of these lipoproteins&#46; Dividing the concentration of TG by 5 if levels are expressed in mg&#47;dL or by 2&#46;2 if they are expressed in mmol&#47;L allows us to calculate TG-rich residual lipoprotein cholesterol&#46; A level &#62;30<span class="elsevierStyleHsp" style=""></span>mg&#47;dL &#40;&#62;0&#46;3<span class="elsevierStyleHsp" style=""></span>mmol&#47;L&#41; indicates that there is an excess of the said cholesterol&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">&#8211;</span></span><p id="par0105" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Non-HDL-c is the appropriate therapeutic target for controlling CVR in patients with atherogenic dyslipidaemia&#46; Although apoB is the ideal marker as it is correlated well with non-HDL-c&#44; it may not be generally available for routine use&#46; Both parameters are highly stable for calculating CVR in cases of atherogenic dyslipidaemia and its associated alterations&#46;</span></p></li></ul></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">The treatment of atherogenic dyslipidaemia</span><p id="par0110" class="elsevierStylePara elsevierViewall">Atherogenic dyslipidaemia is an extremely important entity that clearly contributes to the residual risk after treatment with statins&#46; This dyslipidaemia is under-diagnosed&#44; under-treated and under-controlled&#46; It is particularly relevant in patients at high CVR and those with abdominal obesity&#44; metabolic syndrome and diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">18</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">It is necessary to consider the treatment of this entity based on the available scientific evidence&#44; to improve how it is treated as well as patient adherence&#46;</p><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Lifestyle changes</span><p id="par0120" class="elsevierStylePara elsevierViewall">The first measures to reduce CVR in all patients are a healthy diet&#44; regular physical exercise and smoking cessation&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">The Mediterranean diet&#44; with a reduction in total calorie intake in case of weight gain or abdominal obesity&#44; is accompanied by clear cardiovascular benefits and increased longevity&#46; As well as its beneficial effects on the lipid profile&#44; it also has positive effects on hypertension and hyperglycaemia&#46; The consumption of alcohol must be moderated or avoided in cases of moderate to severe hypertriglyceridaemia&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Aerobic physical exercise too is primordial in atherogenic dyslipidaemia and in the prevention and treatment of metabolic syndrome&#44; hyperglycaemia&#44; diabetes and cardiovascular disease&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pharmacological treatment</span><p id="par0135" class="elsevierStylePara elsevierViewall">As the majority of patients with atherogenic dyslipidaemia are at high or very high risk of cardiovascular disease&#44; different lipid lowering drugs must be combined with lifestyle changes&#46;</p><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Statins</span><p id="par0140" class="elsevierStylePara elsevierViewall">Treatment with statins will start&#44; selecting the type and dose necessary to achieve the therapeutic objective in terms of the required reduction in LDLc&#46; The benefits of treatment with statins are well-known&#44; and they have been clearly proven&#46; A reduction of 1<span class="elsevierStyleHsp" style=""></span>mmol&#47;L &#40;approximately 39<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; in LDLc is associated with a 21&#37; fall in the incidence of severe cardiovascular episodes and a 23&#37; fall in coronary accidents&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">19</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">It is relevant that treatment with low power statins during 10 years in subjects at low CVR has been associated with a 23&#37; reduction in non-mortal episodes of myocardial infarct&#46; However&#44; this reduction amounted to 53&#37; when more powerful statins were used&#44; including a significant reduction in cardiovascular events&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">20&#44;21</span></a> Statins are the first pharmacological treatment to be used in patients with atherogenic dyslipidaemia&#44; as a fall of 1<span class="elsevierStyleHsp" style=""></span>mmol&#47;L &#40;39<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41; in residual cholesterol is also associated with an important reduction in cardiovascular events&#44; similar to what has been observed with the reduction in LDLc&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">22</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Fibrates</span><p id="par0150" class="elsevierStylePara elsevierViewall">Once treatment with statins has achieved the target LDLc level&#44; there is still an unacceptably high risk of cardiovascular events due to the presence of the main components of atherogenic dyslipidaemia &#40;hypertriglyceridaemia and reduced HDLc&#41;&#46; Administering fibrates under these conditions corrects these lipid alterations and has additional cardiovascular benefits&#46; Fibrates have been shown to be beneficial in primary and secondary prevention studies as well as in the diabetic population&#44; above all in the subgroups with atherogenic dyslipidaemia or one of its components&#44; with a fall of 28&#8211;30&#37; in cardiovascular events&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">23&#44;24</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">In the case of fibrate contraindication or intolerance and with raised TG&#44; omega-3 fatty acids may be beneficial in these patients&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">25</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Fibrate-induced lipid changes are explained by modifications in the expressivity of several genes involved in lipid metabolism&#44; through &#945; receptors activated by peroxisome proliferation&#44; with a fall in TG of 20&#8211;50&#37;&#44; in LDLc of 5&#8211;20&#37; &#40;with a reduction in small and dense LDL particles&#41; and an increase in HDLc of from 5&#37; to 20&#37;&#46; These effects depend on basal concentrations<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">11</span></a> and are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">26</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0165" class="elsevierStylePara elsevierViewall">Fenofibrate is the safest fibrate for association with a statin&#58; adding it achieves a stronger cholesterol-lowering effect and control of non-HDL-c&#44; TG and HDLc&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Unlike what occurs with gemfibrozil&#44; the combination of fenofibrate and a statin has shown an excellent safety profile in all of the clinical studies&#44; which include a large number of patients and prolonged treatment&#46; Additionally&#44; the effects of the fenofibrate&#8211;statin association on raised muscle or hepatic enzymes&#44; or on the transitory increase in creatinine&#44; do not differ from what has been observed in monotherapy regimes&#44; so that the reversibility of its effects can be checked&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The FIRST study&#44; which compared the effects of fibrates in subjects treated with atorvastatin on intima-media carotid artery thickness&#44; found a significant reduction in the group treated with fibrates&#44; especially the subjects with triglycerides &#62;170<span class="elsevierStyleHsp" style=""></span>mg&#47;dL and in those with greater arterial intima-media thickness in the basal situation&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">27</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Another work that supports the benefit of treatment with fenofibrate together with statins in subjects with metabolic syndrome is a prospective 5-year study with a large number of patients&#46; This showed a reduction in the combined objective &#40;ischemic coronary disease&#44; cerebral ischemic disease and cardiovascular death&#41; in 36&#37; of the group with added fenofibrate in comparison with the placebo&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">28</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">The main clinical evidence for treatment with fenofibrate is shown in <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">16&#44;29</span></a></p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Extralipid effects of fenofibrate</span><p id="par0190" class="elsevierStylePara elsevierViewall">The results of clinical studies with fenofibrate indicate that as well as changes in the lipid profile&#44; it has other protective vascular effects such as increasing the expression of nitric oxide and reducing oxidative stress&#46; Fibrates have an anti-inflammatory action as they attenuate the production of inflammatory cytokines&#46; Fenofibrate complements this anti-inflammatory action by significantly reducing reactive C protein&#44; the CD40 ligand&#44; monocyte-1 chemotactic protein and the macrophage stimulant factor&#46; It also reduces the plasma concentrations of fibrinogen by up to 20&#37;&#44; thrombin-antithrombin complexes and plasminogen-1 activator inhibitor&#46; Another important extralipid effect is the slowing down of the progression of diabetic retinopathy&#44; independently of glycemic and lipid control&#46; Additionally&#44; these studies indicate that fenofibrate plays a protective role in nephropathy and diabetic neuropathy&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">29</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">The algorithm shown in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> is based on these facts&#44; for the treatment of atherogenic dyslipidaemia and the control of its associated CVR&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Consensus points in the treatment of atherogenic dyslipidaemia</span><p id="par0200" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">&#8211;</span></span><p id="par0205" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Changes in lifestyle&#44; a lipid reducing diet with appropriate calories for weight control&#44; physical exercise and smoking cessation are highly effective in all patients and are the first step in managing atherogenic dyslipidaemia&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">&#8211;</span></span><p id="par0210" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Following changes in lifestyle&#44; statins are the effective and safe initial treatment for the prevention of cardiovascular risk&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">&#8211;</span></span><p id="par0215" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Patients with hypertriglyceridaemia and low HDLc&#44; that is&#44; with atherogenic dyslipidaemia&#44; would benefit from combined statin&#8211;fenofibrate therapy&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">&#8211;</span></span><p id="par0220" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Clinical practice guides and the European Medicines Agency indicate fenofibrate for the treatment of mixed hyperlipidaemia together with a statin when TG and non-HDLc are not properly controlled&#46;</span></p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel"><span class="elsevierStyleItalic">&#8211;</span></span><p id="par0225" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">The evidence for the clinical benefit and safety of the statin&#8211;fenofibrate association is solid&#46; The combination of both drugs in a single tablet simplifies the dosage and may aid adherence over the long term&#46;</span></p></li></ul></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conflict of interests</span><p id="par0230" class="elsevierStylePara elsevierViewall">This is a Spanish Arteriosclerosis Society workgroup and it receives financial support from <span class="elsevierStyleGrantSponsor" id="gs1">Mylan</span>&#46;</p></span></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Ascaso JF&#44; Mill&#225;n J&#44; Hern&#225;ndez-Mijares A&#44; Blasco M&#44; Brea &#193;&#44; D&#237;az &#193;&#44; et al&#46; Dislipidemia aterog&#233;nica 2019&#46; Documento de consenso del Grupo de Dislipidemia Aterog&#233;nica de la Sociedad Espa&#241;ola de Arteriosclerosis&#46; Clin Investig Arterioscler&#46; 2020&#59;32&#58;120&#8211;125&#46;</p>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">apoB&#58; apolipoprotein B&#59; non-HDL-c&#58; non-HDL cholesterol &#40;total cholesterol minus HDL cholesterol&#41;&#59; HDLc&#58; high density lipoprotein cholesterol&#59; CVR&#58; cardiovascular risk&#59; TG&#58; triglycerides&#46;</p>"
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          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">HDLc&#58; high density lipoprotein cholesterol&#59; LDLc&#58; low density lipoprotein cholesterol&#59; LDL&#58; low density lipoproteins&#59; TG&#58; triglycerides&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t">TG&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;40<span class="elsevierStyleHsp" style=""></span>mg&#47;dL in men and &#60;45<span class="elsevierStyleHsp" style=""></span>mg&#47;dL in women&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">LDLc&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;100<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Non-HDL-c&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;130<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TC&#47;HDLc&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;5 in men and &#62;4&#46;5 in women&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Small dense LDL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">TG&#47;HDLc &#62;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2310909.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Atherogenic dyslipidaemia&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">ApoB&#58; apolipoprotein B&#59; non-HDL-c&#58; cholesterol bound to atherogenic lipoproteins &#40;total cholesterol minus high density lipoprotein cholesterol&#41;&#59; HDLc&#58; high density lipoprotein cholesterol&#59; TC&#58; total cholesterol&#59; CV&#58; cardiovascular&#59; DM&#58; diabetes mellitus&#59; DM1&#58; type 1 diabetes mellitus&#59; PAD&#58; peripheral arterial disease&#59; CKD&#58; chronic kidney disease&#59; CVD&#58; cardiovascular disease&#59; eFG&#58; estimated glomerular filtrate&#59; FCVR&#58; cardiovascular risk factor&#59; W&#58; men&#59; FH&#58; family hypercholesterolemia&#59; AMI&#58; acute myocardial infarct&#59; TOL&#58; target organ lesion&#59; W&#58; women&#59; AP&#58; arterial pressure&#59; ACS&#58; acute coronary syndrome&#59; SCORE&#58; European societies risk of cardiovascular death score&#59; TG&#58; triglycerides&#59; TIA&#58; transitory cerebral ischemia&#46;</p>"
          "tablatextoimagen" => array:2 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Primary objectives</th></tr><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Primary objective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Non-HDL-c &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">ApoB &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Moderate CV risk</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;130&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>DM1 &#60;35 years or DM2 &#60;50 years&#44; duration &#60;10 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>SCORE 1&#8211;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">High CV risk</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1 severe FCVR &#40;TC &#62;310<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; LDLc &#62;190<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; AP &#8805;180&#47;110<span class="elsevierStyleHsp" style=""></span>mmHg&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>FH without another FCVR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>DM without TOL&#44; with &#8805;10 years evolution or with 1 FCVR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CKD eFG 30&#8211;59<span class="elsevierStyleHsp" style=""></span>mL&#47;min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>SCORE 5&#8211;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Very high CV risk</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Documented DCV&#58; clinical &#40;ACS&#44; AMI&#44; angina&#44; revascularisation&#44; ictus or TIA&#44; PAD&#41; or unmistakeable image &#40;plaque &#62;50&#37; with any im technique&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>DM with lesion target organ or 1 of the 3 major FCVR or DM1 &#62;20 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CKD-eFG &#60;30<span class="elsevierStyleHsp" style=""></span>mL&#47;min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>SCORE &#8805;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>FH with CVD or with 1 major FCVR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Secondary objectives&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TG &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HDLc &#40;mg&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">After achieving the primary objective</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#62;40<span class="elsevierStyleHsp" style=""></span>H&#62;45<span class="elsevierStyleHsp" style=""></span>W&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab2310907.png"
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          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Lipid objectives in atherogenic dyslipidaemia&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
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          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">apoA-I&#58; apolipoprotein A-I&#59; apoA-II&#58; apolipoprotein A-II&#59; apoC-III&#58; apolipoprotein C-III&#59; apoA-V&#58; apolipoprotein A-V&#59; CETP&#58; cholesterol esters transport protein&#59; HDL&#58; high density lipoproteins&#59; LDL&#58; low density lipoproteins&#59; LPL&#58; lipoprotein lipase&#59; TG&#58; triglycerides&#59; VLDL&#58; very low density lipoproteins&#46;</p>"
          "tablatextoimagen" => array:1 [
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Mechanisms&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Reduction in TG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increasing lipolysis &#40;increasing LPL activity&#44; the synthesis of apoA-V and reducing apoC-III synthesis&#41;Increasing plasma clearing of TG-rich lipoproteinsReducing the availability of fatty acids &#40;reducing synthesis de novo and increasing oxidation&#41; and therefore the synthesis of TG and VLDL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increasing HDL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Increasing the synthesis of apoA-I and apoA-IIReducing CETP activity and therefore the transfer of cholesterol to the VLDL and of TG to the HDL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Changes in LDL particle phenotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Inducing a change of small dense LDL particles&#44; especially atherogenic ones&#44; to ones that are larger and less dense&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab2310908.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Lipid effects of fibrates&#46;</p>"
        ]
      ]
      4 => array:8 [
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        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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            "identificador" => "at4"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Non-HDL-c&#58; cholesterol bound to atherogenic lipoproteins &#40;total cholesterol minus high density lipoprotein cholesterol&#41;&#59; HDLc&#58; high density lipoprotein cholesterol&#59; LDLc&#58; low density lipoprotein cholesterol&#59; CVD&#58; cardiovascular disease&#59; TG&#58; triglycerides&#46;</p>"
          "tablatextoimagen" => array:1 [
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                0 => """
                  <table border="0" frame="\n
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                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
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                  \t\t\t\t">Consider treatment with fibrates for the primary prevention of CVD in patients at high cardiovascular risk and for secondary prevention in those with atherogenic dyslipidaemia&#44; with normal LDLc or non-HDL-c&#44; and in general after treatment with a statin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Evidence class BRecommendation IIb&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">In diabetic patients under treatment with statins&#44; for primary as well as secondary prevention&#44; fenofibrate will be used if TG levels are higher than 200<span class="elsevierStyleHsp" style=""></span>mg&#47;dL with or without low HDLc&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evidence class BRecommendation IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The combination of fenofibrate&#8211;statin is the safest of the fibrate-statin combinations which are available&#44; due to the lower probability of severe adverse effects&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evidence class ARecommendation IIa&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fenofibrate brings about changes in the size of LDL and HDL particles&#44; improving endothelial dysfunction and has anti-inflammatory effects&#44; reducing thrombogenesis and playing a protective role in diabetic retinopathy&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Evidence class CRecommendation&#58; consider for use&nbsp;\t\t\t\t\t\t\n
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                  """
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          "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Evidence for treatment with fibrates&#46;</p>"
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      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
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                            0 => "J&#46; Ascaso"
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                  "host" => array:1 [
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                        0 => array:2 [
                          "etal" => true
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                            0 => "F&#46; Soriguer"
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                    0 => array:2 [
                      "doi" => "10.1186/s12933-016-0415-4"
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                        0 => array:2 [
                          "etal" => false
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                            0 => "J&#46; Mill&#225;n N&#250;&#241;ez-Cortes"
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                        0 => array:2 [
                          "etal" => true
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                            0 => "J&#46; Mill&#225;n"
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                            2 => "A&#46; Mu&#241;oz"
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                        0 => array:2 [
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                            0 => "J&#46;F&#46; Ascaso"
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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                            0 => "F&#46; Mach"
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            ]
            9 => array:3 [
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              "etiqueta" => "10"
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Article information

ISSN: 25299123
Original language: English

DOI:10.1016/j.artere.2020.05.002

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Year/Month	Html	Pdf	Total

2024 November	6	1	7
2024 October	29	9	38
2024 September	24	10	34
2024 August	35	12	47
2024 July	29	7	36
2024 June	22	3	25
2024 May	18	6	24
2024 April	18	4	22
2024 March	27	7	34
2024 February	40	4	44
2024 January	21	4	25
2023 December	21	9	30
2023 November	26	2	28
2023 October	34	8	42
2023 September	17	3	20
2023 August	19	8	27
2023 July	9	7	16
2023 June	9	1	10
2023 May	8	4	12
2023 April	11	4	15
2023 March	12	0	12
2023 February	14	5	19
2023 January	19	6	25
2022 December	14	12	26
2022 November	24	12	36
2022 October	23	9	32
2022 September	18	15	33
2022 August	20	10	30
2022 July	21	7	28
2022 June	15	11	26
2022 May	17	4	21
2022 April	20	9	29
2022 March	21	6	27
2022 February	12	1	13
2021 April	1	0	1
2021 February	1	2	3
2021 January	1	2	3

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